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研究生:黃雍協
研究生(外文):Yuan-Shieh Huang
論文名稱:油酸處理對大鼠心肌細胞間隙接合及肌原纖維之影響
論文名稱(外文):Effects of Oleic acid on Gap Junctions and Myofibrils in Rat Cardiomyocytes
指導教授:王淑美王淑美引用關係
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:解剖學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2007
畢業學年度:95
語文別:中文
論文頁數:102
中文關鍵詞:油酸間隙接合去組合蛋白激酶CPTP-PEST緻密斑去組合rhoAcofilin
外文關鍵詞:oleic acidgap junction disassemblyPKCepsilonPTP-PESTfocal adhesion disassemblyrhoAcofilin
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心肌缺氧及糖尿病的病人,脂質的代謝平衡受到改變,血液中的不飽和游離脂肪酸濃度會大幅的增加,尤其是油酸(oleic acid)。增高的脂肪酸在心肌細胞內酯化成三酸甘油酯,以脂肪小滴(lipid droplets)的型式堆積在心肌細胞的細胞質。脂肪小滴的堆積會降低心輸出量及干擾間隙接合功能。然而至目前為止,脂肪小滴的堆積對心肌細胞損傷的機制仍不清楚。本研究的第一部分即是探討油酸對培養的新生大白鼠心肌細胞間隙接合的影響及機轉。當細胞以油酸處理後,培養的心肌細胞自發性收縮速率會減低,但不影響細胞存活度。除此之外,位在細胞接合處的Cx43的染色分布也減少,顯示間隙接合的去組合。以scrape loading方法分析間隙接合的功能,結果顯示油酸降低間隙接合所調節的細胞間溝通。已知Cx43的磷酸化可以直接調控間隙接合的組合或去組合。西方墨點分析法(Western blot analysis)証明油酸會引起Cx43 Ser-368磷酸化的增加,這個位置的磷酸化增加已知可能參與間隙接合去組合。Protein kinase C(PKC)參與Cx43 Ser-368磷酸化的增加,因為使用PKC的抑制劑可以阻止油酸引起Cx Ser-368磷酸化的升高。共軛焦的影像顯示PKCe及PKCa分別與Cx43在間隙接合共位(colocalization),油酸處理後使得位在細胞接合處之PKCe及PKCa分布減少。以含有BSA新鮮培養基置換油酸,繼續培養24小時後,油酸引起兩相鄰細胞間蛋白質分布的改變可回復。進一步以免疫沈澱分析法証實Cx43分別與PKCe及PKCa有生化上的連結,當細胞以油酸處理後,不影響這些蛋白質的交互作用,暗示Cx43與PKCe /PKCa有穩定的連結並導致油酸處理後,因為細胞膜上的間隙接合分布減少,使原本與間隙接合共位的PKCe 及PKCa由細胞膜脫位至細胞質。接著檢驗PKC的異構物(isoforms),分別加入PKCe以及PKCa的抑制劑,實驗結果發現只有在加入PKCe抑制劑後,可以有效阻止油酸引起的Cx43 Ser-368磷酸化的增加和間隙接合的去組合,並且恢復間隙接合細胞間溝通的能力。以上結果顯示油酸可能藉由活化PKCe,使得Cx43 Ser-368磷酸化的升高,進而導致間隙接合去組合。本研究的第二部分則是觀察油酸對肌原纖維的影響及其機轉。免疫螢螢光染色的結果顯示油酸引發肌節排列紊亂,肌原纖維發生去組合的現象。因為緻密斑(focal adhesions)參與肌原纖維的組合,我們接著檢驗油酸對緻密斑結構的影響。免疫螢光染色的結果顯示,油酸造成integrin b1D、vinculin及paxillin抗體所標示的緻密斑及肋狀體(costameres)結構排列的紊亂及喪失,而且這三個蛋白質的表現均下降。這些變化的時間點早於肌原纖維的去組合,顯示緻密斑參與油酸引發肌原纖維的去組合。將油酸移除後,油酸對於緻密斑及肌原纖維結構的影響可回復。我們進一步檢驗緻密斑蛋白的磷酸化表現。油酸引起FAK與paxillin的酪胺酸去磷酸化,及integrin b1D、paxillin及muscle actin蛋白質表現量下降。而此效應可被酪胺酸去磷酸酶抑制劑原釩酸鈉(sodium orthrovandate)阻斷,同時也可以阻斷油酸引發之肌原纖維去組合,顯示油酸可能活化酪胺酸去磷酸酶。先前的研究指出,FAK及paxillin為PTP-PEST(一種酪胺酸去磷酸酶)的受質,可將此二蛋白去磷酸化。本研究發現油酸引發PTP-PEST蛋白質的向上調節,暗示PPTP-PEST可能參與緻密斑蛋白的去磷酸酸化,引起緻密斑及肋狀體的瓦解,進而導致肌原纖維的去組合。另外,RhoA/cofilin的路徑也可調控肌原纖維的去組合。Cofilin是一種actin-severing蛋白,RhoA會使cofilin的磷酸化增加並抑制其活性,促進actin filament的組合,相反的,RhoA活性降低則減少cofilin磷酸化並引起cofilin活性增加並導致actin filament的去聚合。油酸會減低RhoA的活性及cofilin的磷酸化,此結果暗示油酸導致cofilin活性的增強也許與肌節構造去組合有密切的因果關係。綜合以上的結果,油酸可以透過不同的機制,分別引起間隙接合及肌原纖維的去組合。油酸活化PKCe,引起Cx43 S368磷酸化增加,導致間隙接合去組合。另外,油酸也可能藉由PTP-PEST,參與paxillin及FAK去磷酸化,引起緻密斑去組合,或是直接降低RhoA-cofilin的訊息傳遞,造成actin filaments瓦解,進而引起明帶(I-bands)及其它肌節構造的去組合。
In ischemic and diabetic patients, plasma levels of nonesterified free fatty acids, such as oleic acid (OA), are increased, and the free fatty acids are accumulated as lipid droplets in the cytoplasm of cardiomyocytes, resulting in interference in gap junction-mediated intercellular communication and cardiac output. However, the mechanism of OA-induced electrical uncoupling and contractile dysfunction in cardiomyocytes remains unclear. Therefore, the first section of this study was designed to investigate the effects of OA on gap junctions in cultured neonatal rat cardiomyocytes. OA reduced the spontaneous contraction rates of cultured cardiomyocytes in a time-dependent manner without affecting the cell viability. In addition, Cx43 expression at cell-cell junction decreased after OA treatment, suggesting the disassembly of gap junction. Functional assays by scrape-loading dye transfer assay further demonstrated that OA decreased gap junction-mediated intercellular communication. It is known that Cx43 phosphorylation can modulate the assembly and disassembly of gap junctions. Western blot analysis showed that OA induced Cx43 Ser368 phosphorylation. The phosporylation of this residue has been shown to be involved in gap junction disassembly. PKC participated in Cx43 phosphorylation on Ser368, since PKC inhibitor, calphostin C prevented OA-induced Cx43 Ser368 phosphorylation. Staining for PKCe and PKCa, which were shown to colocalize with Cx43 in confocal images, decreased with increased duration of OA treatment. The effects of OA on these distributional changes at cell junctions were reversed by 24 h incubation in fresh culture medium devoid of OA. Immunoprecipitation assays confirmed the biochemical binding between Cx43 and PKCe/PKCa, and this protein-protein interaction was not affected by OA. This observation may provide the basis for simultaneous detachment of Cx and PKCe/PKCa from the cell-cell junction to the cytosol upon OA stimulation. In order to determine whether PKCε or PKCα was involved in OA-induced Ser368 phosphorylation, we used the PKCε inhibitor, eV1-2, and the PKCα inhibitor, Go6976, and found that only eV1-2 had a significant effect in preventing OA-induced Cx43 Ser368 phosphorylation, gap junction disassembly, and gap junction-mediated intercellular communication. These data suggest that selective activation of PKCε by OA is required for OA-induced Cx43 Ser368 phosphorylation, leading to gap junction disassembly. The second section of this study investigated the effects of OA on contractile apparatus and the signaling pathways involved in this event. OA treatment disrupted myofibrils, as revealed by the disorganization of several sarcomeric proteins. Since focal adhesions (FAs) are implicated in myofibril assembly, we examined structural changes of FAs after OA treatment. Immunofluorescence studies with antibodies against FA proteins (vinculin, integrin b1D, and paxillin) showed that FAs and costameres disintegrated or disappeared after OA treatment and that the changes in FA proteins occurred prior to myofibril disassembly. The effects of OA on FAs and myofibrils were reversed after removal of OA. OA decreased expression of integrin b1D, paxillin, vinculin, and actin, and induced tyrosine dephosphorylation of focal adhesion kinase (FAK) and paxillin. These effects were blocked by pretreatment with sodium orthovanadate, a protein tyrosine phosphatase (PTP) inhibitor. This inhibitor also prevented OA-induced myofibril disassembly, indicating the involvement of PTP in myofibril disassembly. Furthermore, OA increased protein levels of PTP-PEST. The upregulation of this phosphatase correlated with the tyrosine dephosphorylation of paxillin and FAK, which are targets for PTP-PEST. In addition, OA decreased RhoA activity and the phosphorylation of cofilin, a downstream target of RhoA. Cofilin dephosphorylation activated cofilin and led to the depolymerization of F-actin, which might provide the other potential mechanism for myofibril disassembly in addition to FA disassembly. Taken together, OA induced disassembly of gap junctions and myofibrils through different signaling pathways. OA-induced Cx43 Ser368 phosphorylation is mediated by PKCe activation, which might be responsible for OA-induced gap junctional disassembly. In addition, OA also induced tyrosine dephosphorylation of paxillin and FAK by PTP-PEST, which resulted in FA disassembly and subsequent myofibril disruption. In addition, OA induced cofilin activation by decreasing RhoA activity and cofilin phosphorylation levels, which might lead to depolymerization of actin filaments and disassembly of I-bands and other sarcomeric structures.
口試委員會審定書---------------------------------------------------Ⅰ
誌謝----------------------------------------------------------------------Ⅱ
中文摘要----------------------------------------------------------------Ⅲ
英文摘要----------------------------------------------------------------Ⅵ
第一章:文獻回顧----------------------------------------------------1
第二章:油酸引發大鼠心肌細胞間隙接合去組合之機制
第一節 摘要------------------------------------------------------7
第二節 緒論 ----------------------------------------------------8
第三節 材料及方法--------------------------------------------11
第四節 結果 ----------------------------------------------------17
第五節 討論 ----------------------------------------------------22
第六節 參考文獻 ----------------------------------------------27
第七節 圖片說明 ----------------------------------------------31
第三章:油酸引發大鼠心肌細胞肌原纖維去組合之機制
第一節 摘要 ----------------------------------------------------54
第二節 緒論 ----------------------------------------------------56
第三節 材料及方法--------------------------------------------62
第四節 結果 ----------------------------------------------------67
第五節 討論 ----------------------------------------------------71
第六節 參考文獻 ----------------------------------------------76
第七節 圖片說明 ----------------------------------------------82
第四章:結論及展望 ----------------------------------------------98
第一節 參考文獻----------------------------------------------101
第二節 模式圖 ----------------------------------------------102
Aylsworth, C.F., J.E. Trosko, C.C. Chang, K. Benjamin, and E. Lockwood. 1989. Synergistic inhibition of metabolic cooperation by oleic acid or 12-0-tetradecanoylphorbol-13-acetate and dichlorodiphenyltrichlorethane (DDT) in Chinese hamster V79 cells: implication of a role for protein kinase C in the regulation of gap junctional intercellular communication. Cell Biol Toxicol. 5:27-37.
Bilheimer, D.W., L.M. Buja, R.W. Parkey, F.J. Bonte, and J.T. Willerson. 1978. Fatty acid accumulation and abnormal lipid deposition in peripheral and border zones of experimental myocardial infarcts. J Nucl Med. 19:276-83.
Borradaile, N.M., and J.E. Schaffer. 2005. Lipotoxicity in the heart. Curr Hypertens Rep. 7:412-7.
Burton, K.P., L.M. Buja, A. Sen, J.T. Willerson, and K.R. Chien. 1986. Accumulation of arachidonate in triacylglycerols and unesterified fatty acids during ischemia and reflow in the isolated rat heart. Correlation with the loss of contractile function and the development of calcium overload. Am J Pathol. 124:238-45.
Christoffersen, C., E. Bollano, M.L. Lindegaard, E.D. Bartels, J.P. Goetze, C.B. Andersen, and L.B. Nielsen. 2003. Cardiac lipid accumulation associated with diastolic dysfunction in obese mice. Endocrinology. 144:3483-90.
Diaz-Guerra MJ., M. Junco, and L. Bosca. 1991. Oleic acid promotes changes in the subcellular distribution of protein kinase C in isolated hepatocytes. J Biol Chem. 266:23568-76.
Girard, J. 2000. [Fatty acids and beta cells]. Diabetes Metab. 26 Suppl 3:6-9.
Goldberg, E.M., and R. Zidovetzki. 1998. Synergistic effects of diacylglycerols and fatty acids on membrane structure and protein kinase C activity. Biochemistry. 37:5623-32.
Hirschi, K.K., B.N. Minnich, L.K. Moore, and J.M. Burt. 1993. Oleic acid differentially affects gap junction-mediated communication in heart and vascular smooth muscle cells. Am J Physiol. 265:C1517-26.
Lu, G., E.L. Greene, T. Nagai, and B.M. Egan. 1998a. Reactive oxygen species are critical in the oleic acid-mediated mitogenic signaling pathway in vascular smooth muscle cells. Hypertension 32:1003-10.
Lu, G., K.E. Meier, A.A..Jaffa, S.A. Rosenzweig, and B.M. Egan. 1998b. Oleic acid and angiotensin II induce a synergistic mitogenic response in vascular smooth muscle cells. Hypertension 31:978-85.
Maekawa, M., T. Ishizaki, S. Boku, N. Watanabe, A. Fujita, A. Iwamatsu, T. Obinata, K. Ohashi, K. Mizuno, and S. Narumiya. 1999. Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Science 285:895-8.
Murakami K. and A. Routtenberg. 1985. Direct activation of purified protein kinase C by unsaturated fatty acids (oleate and arachidonate) in the absence of phospholipids and Ca2+. FEBS Lett 192:189-93.
Myrmel, T., K. Forsdahl, and T.S. Larsen. 1992. Triacylglycerol metabolism in hypoxic, glucose-deprived rat cardiomyocytes. J Mol Cell Cardiol. 24:855-68.
Nielsen, L.B., E.D. Bartels, and E. Bollano. 2002. Overexpression of apolipoprotein B in the heart impedes cardiac triglyceride accumulation and development of cardiac dysfunction in diabetic mice. J Biol Chem. 277:27014-20.
Riemersma, R.A. 1987. Raised plasma non-esterified fatty acids (NEFA) during ischaemia: implications for arrhythmias. Basic Res Cardiol. 82 Suppl 1:177-86.
Schadinger, S.E., N.L. Bucher, B.M. Schreiber, and S.R. Farmer. 2005. PPARgamma2 regulates lipogenesis and lipid accumulation in steatotic hepatocytes. Am J Physiol Endocrinol Metab. 288:E1195-205.
Sharma, S., J.V. Adrogue, L. Golfman, I. Uray, J. Lemm, K. Youker, G.P. Noon, O.H. Frazier, and H. Taegtmeyer. 2004. Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart. Faseb J. 18:1692-700.
van Bilsen, M., G.J. van der Vusse, P.H. Willemsen, W.A. Coumans, T.H. Roemen, and R.S. Reneman. 1989. Lipid alterations in isolated, working rat hearts during ischemia and reperfusion: its relation to myocardial damage. Circ Res. 64:304-14.
Wang SM, Y.J. Tsai, M.J. Jiang, and Y.Z. Tseng 1997. Studies on the function of rho A protein in cardiac myofibrillogenesis. J Cell Biochem. 66:43-53.

Aylsworth, C.F., J.E. Trosko, C.C. Chang, K. Benjamin, and E. Lockwood. 1989. Synergistic inhibition of metabolic cooperation by oleic acid or 12-0-tetradecanoylphorbol-13-acetate and dichlorodiphenyltrichlorethane (DDT) in Chinese hamster V79 cells: implication of a role for protein kinase C in the regulation of gap junctional intercellular communication. Cell Biol Toxicol. 5:27-37.
Beardslee, M.A., D.L. Lerner, P.N. Tadros, J.G. Laing, E.C. Beyer, K.A. Yamada, A.G. Kleber, R.B. Schuessler, and J.E. Saffitz. 2000. Dephosphorylation and intracellular redistribution of ventricular connexin43 during electrical uncoupling induced by ischemia. Circ Res. 87:656-62.
Bendahhou, S., T.R. Cummins, and W.S. Agnew. 1997. Mechanism of modulation of the voltage-gated skeletal and cardiac muscle sodium channels by fatty acids. Am J Physiol. 272:C592-600.
Bilheimer, D.W., L.M. Buja, R.W. Parkey, F.J. Bonte, and J.T. Willerson. 1978. Fatty acid accumulation and abnormal lipid deposition in peripheral and border zones of experimental myocardial infarcts. J Nucl Med. 19:276-83.
Bowling, N., X. Huang, G.E. Sandusky, R.L. Fouts, K. Mintze, M. Esterman, P.D. Allen, R. Maddi, E. McCall, and C.J. Vlahos. 2001. Protein kinase C-alpha and -epsilon modulate connexin-43 phosphorylation in human heart. J Mol Cell Cardiol. 33:789-98.
Budunova, I.V., L.A. Mittelman, and J. Miloszewska. 1994. Role of protein kinase C in the regulation of gap junctional communication. Teratog Carcinog Mutagen. 14:259-70.
Burton, K.P., L.M. Buja, A. Sen, J.T. Willerson, and K.R. Chien. 1986. Accumulation of arachidonate in triacylglycerols and unesterified fatty acids during ischemia and reflow in the isolated rat heart. Correlation with the loss of contractile function and the development of calcium overload. Am J Pathol. 124:238-45.
Chang, C.H., W.Y. Chey, and T.M. Chang. 2000. Cellular mechanism of sodium oleate-stimulated secretion of cholecystokinin and secretin. Am J Physiol Gastrointest Liver Physiol. 279:G295-303.
Christoffersen, C., E. Bollano, M.L. Lindegaard, E.D. Bartels, J.P. Goetze, C.B. Andersen, and L.B. Nielsen. 2003. Cardiac lipid accumulation associated with diastolic dysfunction in obese mice. Endocrinology. 144:3483-90.
Chung, TH, S.M. Wang, and J.C. Wu. 2004. 17beta-estradiol reduces the effect of metabolic inhibition on gap junction intercellular communication in rat cardiomyocytes via the estrogen receptor. J Mol Cell Cardiol. 37:1013-22.
Darrow, B.J., J.G. Laing, P.D. Lampe, J.E. Saffitz, and E.C. Beyer. 1995. Expression of multiple connexins in cultured neonatal rat ventricular myocytes. Circ Res. 76:381-7.
Doble, B.W., X. Dang, P. Ping, R.R. Fandrich, B.E. Nickel, Y. Jin, P.A. Cattini, and E. Kardami. 2004. Phosphorylation of serine 262 in the gap junction protein connexin-43 regulates DNA synthesis in cell-cell contact forming cardiomyocytes. J Cell Sci. 117:507-14.
Doble, B.W., P. Ping, and E. Kardami. 2000. The epsilon subtype of protein kinase C is required for cardiomyocyte connexin-43 phosphorylation. Circ Res. 86:293-301.
Giepmans, B.N., T. Hengeveld, F.R. Postma, and W.H. Moolenaar. 2001. Interaction of c-Src with gap junction protein connexin-43. Role in the regulation of cell-cell communication. J Biol Chem. 276:8544-9.
Gutstein, D.E., G.E. Morley, D. Vaidya, F. Liu, F.L. Chen, H. Stuhlmann, and G.I. Fishman. 2001. Heterogeneous expression of Gap junction channels in the heart leads to conduction defects and ventricular dysfunction. Circulation. 104:1194-9.
Hirschi, K.K., B.N. Minnich, L.K. Moore, and J.M. Burt. 1993. Oleic acid differentially affects gap junction-mediated communication in heart and vascular smooth muscle cells. Am J Physiol. 265:C1517-26.
Kang, J.X., Y.F. Xiao, and A. Leaf. 1995. Free, long-chain, polyunsaturated fatty acids reduce membrane electrical excitability in neonatal rat cardiac myocytes. Proc Natl Acad Sci U S A. 92:3997-4001.
Laird, D.W., K.L. Puranam, and J.P. Revel. 1991. Turnover and phosphorylation dynamics of connexin43 gap junction protein in cultured cardiac myocytes. Biochem J. 273(Pt 1):67-72.
Lampe, P.D. 1994. Analyzing phorbol ester effects on gap junctional communication: a dramatic inhibition of assembly. J Cell Biol. 127:1895-905.
Lampe, P.D., E.M. TenBroek, J.M. Burt, W.E. Kurata, R.G. Johnson, and A.F. Lau. 2000. Phosphorylation of connexin43 on serine368 by protein kinase C regulates gap junctional communication. J Cell Biol. 149:1503-12.
Lin R, Warn-Cramer BJ, Kurata WE, Lau AF. 2001. v-Src phosphorylation of connexin 43 on Tyr247 and Tyr265 disrupts gap junctional communication. J Cell Biol 154:815-27.
Linden, D.J., F.S. Sheu, K. Murakami, and A. Routtenberg. 1987. Enhancement of long-term potentiation by cis-unsaturated fatty acid: relation to protein kinase C and phospholipase A2. J Neurosci. 7:3783-92.
Lu, G., T.A. Morinelli, K.E. Meier, S.A. Rosenzweig, and B.M. Egan. 1996. Oleic acid-induced mitogenic signaling in vascular smooth muscle cells. A role for protein kinase C. Circ Res. 79:611-8.
Mackay, K., and D. Mochly-Rosen. 2001. Arachidonic acid protects neonatal rat cardiac myocytes from ischaemic injury through epsilon protein kinase C. Cardiovasc Res. 50:65-74.
Misikangas, M., R. Freese, A.M. Turpeinen, and M. Mutanen. 2001. High linoleic acid, low vegetable, and high oleic acid, high vegetable diets affect platelet activation similarly in healthy women and men. J Nutr. 131:1700-5.
Musil, L.S., and D.A. Goodenough. 1991. Biochemical analysis of connexin43 intracellular transport, phosphorylation, and assembly into gap junctional plaques. J Cell Biol. 115:1357-74.
Nagy, J.I., W.E. Li, C. Roy, B.W. Doble, J.S. Gilchrist, E. Kardami, and E.L. Hertzberg. 1997. Selective monoclonal antibody recognition and cellular localization of an unphosphorylated form of connexin43. Exp Cell Res. 236:127-36.
Oyamada, M., E. Tsujii, H. Tanaka, T. Matsushita, and T. Takamatsu. 2001. Abnormalities in gap junctions and Ca2+ dynamics in cardiomyocytes at the border zone of myocardial infarcts. Cell Commun Adhes. 8:335-8.
Pi, Y., and J.W. Walker. 2000. Diacylglycerol and fatty acids synergistically increase cardiomyocyte contraction via activation of PKC. Am J Physiol Heart Circ Physiol. 279:H26-34.
Reaume, A.G., P.A. de Sousa, S. Kulkarni, B.L. Langille, D. Zhu, T.C. Davies, S.C. Juneja, G.M. Kidder, and J. Rossant. 1995. Cardiac malformation in neonatal mice lacking connexin43. Science. 267:1831-4.
Reed, K.E., E.M. Westphale, D.M. Larson, H.Z. Wang, R.D. Veenstra, and E.C. Beyer. 1993. Molecular cloning and functional expression of human connexin37, an endothelial cell gap junction protein. J Clin Invest. 91:997-1004.
Saffitz, J.E., L.M. Davis, B.J. Darrow, H.L. Kanter, J.G. Laing, and E.C. Beyer. 1995. The molecular basis of anisotropy: role of gap junctions. J Cardiovasc Electrophysiol. 6:498-510.
Shibata, Y., M. Kumai, K. Nishii, and K. Nakamura. 2001. Diversity and molecular anatomy of gap junctions. Med Electron Microsc. 34:153-9.
Shin, J.L., J.L. Solan, and P.D. Lampe. 2001. The regulatory role of the C-terminal domain of connexin43. Cell Commun Adhes. 8:271-5.
Song, C., T.M. Vondriska, G.W. Wang, J.B. Klein, X. Cao, J. Zhang, Y.J. Kang, S. D''Souza, and P. Ping. 2002. Molecular conformation dictates signaling module formation: example of PKCepsilon and Src tyrosine kinase. Am J Physiol Heart Circ Physiol. 282:H1166-71.
TenBroek, E.M., P.D. Lampe, J.L. Solan, J.K. Reynhout, and R.G. Johnson. 2001. Ser364 of connexin43 and the upregulation of gap junction assembly by cAMP. J Cell Biol. 155:1307-18.
Vaidya, D., H.S. Tamaddon, C.W. Lo, S.M. Taffet, M. Delmar, G.E. Morley, and J. Jalife. 2001. Null mutation of connexin43 causes slow propagation of ventricular activation in the late stages of mouse embryonic development. Circ Res. 88:1196-202.
van der Vusse, G.J., F.W. Prinzen, M. van Bilsen, W. Engels, and R.S. Reneman. 1987. Accumulation of lipids and lipid-intermediates in the heart during ischaemia. Basic Res Cardiol. 82 Suppl 1:157-67.
Vikhamar, G., E. Rivedal, S. Mollerup, and T. Sanner. 1998. Role of Cx43 phosphorylation and MAP kinase activation in EGF induced enhancement of cell communication in human kidney epithelial cells. Cell Adhes Commun. 5:451-60.
Way, K.J., E. Chou, and G.L. King. 2000. Identification of PKC-isoform-specific biological actions using pharmacological approaches. Trends Pharmacol Sci. 21:181-7.
Wu, JC, R.Y. Tsai, and T.H. Chung. 2003. Role of catenins in the development of gap junctions in rat cardiomyocytes. J Cell Biochem. 88:823-35.
Xu, X., W.E. Li, G.Y. Huang, R. Meyer, T. Chen, Y. Luo, M.P. Thomas, G.L. Radice, and C.W. Lo. 2001. Modulation of mouse neural crest cell motility by N-cadherin and connexin 43 gap junctions. J Cell Biol. 154:217-30.
Yun, MR., J.Y. Lee, H.S. Park, H.J. Heo, J.Y. Park, S.S. Bae, K.W. Hong, S.M. Sung, and C.D. Kim. 2006. Oleic acid enhances vascular smooth muscle cell proliferation via phosphatidylinositol 3-kinase/Akt signaling pathway. Pharmacol Res. 54:97-102.
Zeidman, R., U. Troller, A. Raghunath, S. Pahlman, and C. Larsson. 2002. Protein kinase Cepsilon actin-binding site is important for neurite outgrowth during neuronal differentiation. Mol Biol Cell. 13:12-24.
Zheng, J.S., M.O. Boluyt, X. Long, L. O''Neill, E.G. Lakatta, and M.T. Crow. 1996. Extracellular ATP inhibits adrenergic agonist-induced hypertrophy of neonatal cardiac myocytes. Circ Res. 78:525-35.
Zhou L, E.M. Kasperek, and B.J. Nicholson. 1999. Dissection of the molecular basis of pp60(v-src) induced gating of connexin 43 gap junction channels. J Cell Biol 144:1033-45.

Aikawa, R., T. Nagai, S. Kudoh, Y. Zou, M. Tanaka, M. Tamura, H. Akazawa, H. Takano, R. Nagai, and I. Komuro. 2002. Integrins play a critical role in mechanical stress-induced p38 MAPK activation. Hypertension. 39:233-8.
Altruda, F., P. Cervella, G. Tarone, C. Botta, F. Balzac, G. Stefanuto, and L. Silengo. 1990. A human integrin beta 1 subunit with a unique cytoplasmic domain generated by alternative mRNA processing. Gene. 95:261-6.
Angers-Loustau, A., J.F. Cote, A. Charest, D. Dowbenko, S. Spencer, L.A. Lasky, and M.L. Tremblay. 1999. Protein tyrosine phosphatase-PEST regulates focal adhesion disassembly, migration, and cytokinesis in fibroblasts. J Cell Biol. 144:1019-31.
Aoki H, Izumo S, Sadoshima J 1998. Angiotensin II activates RhoA in cardiac myocytes: a critical role of RhoA in angiotensin II-induced premyofibril formation. Circ Res 82:666-76.
Argraves, W.S., S. Suzuki, H. Arai, K. Thompson, M.D. Pierschbacher, and E. Ruoslahti. 1987. Amino acid sequence of the human fibronectin receptor. J Cell Biol. 105:1183-90.
Belkin, A.M., N.I. Zhidkova, F. Balzac, F. Altruda, D. Tomatis, A. Maier, G. Tarone, V.E. Koteliansky, and K. Burridge. 1996. Beta 1D integrin displaces the beta 1A isoform in striated muscles: localization at junctional structures and signaling potential in nonmuscle cells. J Cell Biol. 132:211-26.
Bilheimer, D.W., L.M. Buja, R.W. Parkey, F.J. Bonte, and J.T. Willerson. 1978. Fatty acid accumulation and abnormal lipid deposition in peripheral and border zones of experimental myocardial infarcts. J Nucl Med. 19:276-83.
Burridge, K., C.E. Turner, and L.H. Romer. 1992. Tyrosine phosphorylation of paxillin and pp125FAK accompanies cell adhesion to extracellular matrix: a role in cytoskeletal assembly. J Cell Biol. 119:893-903.
Burton, K.P., L.M. Buja, A. Sen, J.T. Willerson, and K.R. Chien. 1986. Accumulation of arachidonate in triacylglycerols and unesterified fatty acids during ischemia and reflow in the isolated rat heart. Correlation with the loss of contractile function and the development of calcium overload. Am J Pathol. 124:238-45.
Cai, X.M., B.B. Tao, L.Y. Wang, Y.L. Liang, J.W. Jin, Y. Yang, Y.L. Hu, and X.L. Zha. 2005. Protein phosphatase activity of PTEN inhibited the invasion of glioma cells with epidermal growth factor receptor mutation type III expression. Int J Cancer. 117:905-12.
Calalb MB, T.R. Polte, and S.K. Hanks. 1995. Tyrosine phosphorylation of focal adhesion kinase at sites in the catalytic domain regulates kinase activity: a role for Src family kinases. Mol Cell Biol. 15:954-63.
Chen Y, S.M. Wang, J.C. Wu, and S.H. Huang 2006. Effects of PPARgamma agonists on cell survival and focal adhesions in a Chinese thyroid carcinoma cell line. J Cell Biochem 98:1021-35.
Chiu, H.C., A. Kovacs, D.A. Ford, F.F. Hsu, R. Garcia, P. Herrero, J.E. Saffitz, and J.E. Schaffer. 2001. A novel mouse model of lipotoxic cardiomyopathy. J Clin Invest. 107:813-22.
Christoffersen, C., E. Bollano, M.L. Lindegaard, E.D. Bartels, J.P. Goetze, C.B. Andersen, and L.B. Nielsen. 2003. Cardiac lipid accumulation associated with diastolic dysfunction in obese mice. Endocrinology. 144:3483-90.
Davidson D, Veillette A 2001. PTP-PEST, a scaffold protein tyrosine phosphatase, negatively regulates lymphocyte activation by targeting a unique set of substrates. Embo J 20:3414-26.
de Vries, J.E., M.M. Vork, T.H. Roemen, Y.F. de Jong, J.P. Cleutjens, G.J. van der Vusse, and M. van Bilsen. 1997. Saturated but not mono-unsaturated fatty acids induce apoptotic cell death in neonatal rat ventricular myocytes. J Lipid Res. 38:1384-94.
Defilippi, P., S.F. Retta, C. Olivo, M. Palmieri, M. Venturino, L. Silengo, and G. Tarone. 1995. p125FAK tyrosine phosphorylation and focal adhesion assembly: studies with phosphotyrosine phosphatase inhibitors. Exp Cell Res. 221:141-52.
Fassler, R., J. Rohwedel, V. Maltsev, W. Bloch, S. Lentini, K. Guan, D. Gullberg, J. Hescheler, K. Addicks, and A.M. Wobus. 1996. Differentiation and integrity of cardiac muscle cells are impaired in the absence of beta 1 integrin. J Cell Sci. 109 ( Pt 13):2989-99.
Garton, A.J., and N.K. Tonks. 1994. PTP-PEST: a protein tyrosine phosphatase regulated by serine phosphorylation. Embo J. 13:3763-71.
Goncharova, E.J., Z. Kam, and B. Geiger. 1992. The involvement of adherens junction components in myofibrillogenesis in cultured cardiac myocytes. Development. 114:173-83.
Hagel, M., E.L. George, A. Kim, R. Tamimi, S.L. Opitz, C.E. Turner, A. Imamoto, and S.M. Thomas. 2002. The adaptor protein paxillin is essential for normal development in the mouse and is a critical transducer of fibronectin signaling. Mol Cell Biol. 22:901-15.
Hamadi, A., M. Bouali, M. Dontenwill, H. Stoeckel, K. Takeda, and P. Ronde. 2005. Regulation of focal adhesion dynamics and disassembly by phosphorylation of FAK at tyrosine 397. J Cell Sci. 118:4415-25.
Hanks SK, Ryzhova L, Shin NY, Brabek J. 2003. Focal adhesion kinase signaling activities and their implications in the control of cell survival and motility. Front Biosci 8:d982-96.
Heidkamp, M.C., A.L. Bayer, J.A. Kalina, D.M. Eble, and A.M. Samarel. 2002. GFP-FRNK disrupts focal adhesions and induces anoikis in neonatal rat ventricular myocytes. Circ Res. 90:1282-9.
Heidkamp MC, Bayer AL, Scully BT, Eble DM, Samarel AM. 2003. Activation of focal adhesion kinase by protein kinase C epsilon in neonatal rat ventricular myocytes. Am J Physiol Heart Circ Physiol 285:H1684-96.
Hickson-Bick, D.L., G.C. Sparagna, L.M. Buja, and J.B. McMillin. 2002. Palmitate-induced apoptosis in neonatal cardiomyocytes is not dependent on the generation of ROS. Am J Physiol Heart Circ Physiol. 282:H656-64.
Hilenski, L.L., X.H. Ma, N. Vinson, L. Terracio, and T.K. Borg. 1992. The role of beta 1 integrin in spreading and myofibrillogenesis in neonatal rat cardiomyocytes in vitro. Cell Motil Cytoskeleton. 21:87-100.
Hirschi, K.K., B.N. Minnich, L.K. Moore, and J.M. Burt. 1993. Oleic acid differentially affects gap junction-mediated communication in heart and vascular smooth muscle cells. Am J Physiol. 265:C1517-26.
Hoshijima, M., V.P. Sah, Y. Wang, K.R. Chien, J.H. Brown. 1998. The low molecular weight GTPase Rho regulates myofibril formation and organization in neonatal rat ventricular myocytes. Involvement of Rho kinase. J Biol Chem. 273:7725-30.
Huang, Y.S., Y.Z. Tseng, J.C. Wu, and S.M. Wang. 2004. Mechanism of oleic acid-induced gap junctional disassembly in rat cardiomyocytes. J Mol Cell Cardiol. 37:755-66.
Imanaka-Yoshida, K., M. Enomoto-Iwamoto, T. Yoshida, and T. Sakakura. 1999. Vinculin, Talin, Integrin alpha6beta1 and laminin can serve as components of attachment complex mediating contraction force transmission from cardiomyocytes to extracellular matrix. Cell Motil Cytoskeleton. 42:1-11.
Kaarbo, M, D.I. Crane, W.G. Murrell. 2003. RhoA is highly up-regulated in the process of early heart development of the chick and important for normal embryogenesis. Dev Dyn. 227:35-47.
Kim, Y.Y., C.S. Lim, Y.H. Song, J. Ahnn, D. Park, and W.K. Song. 1999. Cellular localization of alpha3beta1 integrin isoforms in association with myofibrillogenesis during cardiac myocyte development in culture. Cell Adhes Commun. 7:85-97.
Kovacic-Milivojevic, B., F. Roediger, E.A. Almeida, C.H. Damsky, D.G. Gardner, and D. Ilic. 2001. Focal adhesion kinase and p130Cas mediate both sarcomeric organization and activation of genes associated with cardiac myocyte hypertrophy. Mol Biol Cell. 12:2290-307.
Laser M., C.D. Willey, W. Jiang, Gt. Cooper, D.R. Menick, M.R. Zile, D. Kuppuswamy. 2000. Integrin activation and focal complex formation in cardiac hypertrophy. J Biol Chem. 275:35624-30.
Languino, L.R., and E. Ruoslahti. 1992. An alternative form of the integrin beta 1 subunit with a variant cytoplasmic domain. J Biol Chem. 267:7116-20.
Lin, Z.X., S. Holtzer, T. Schultheiss, J. Murray, T. Masaki, D.A. Fischman, and H. Holtzer. 1989. Polygons and adhesion plaques and the disassembly and assembly of myofibrils in cardiac myocytes. J Cell Biol. 108:2355-67.
Maekawa, M., T. Ishizaki, S. Boku, N. Watanabe, A. Fujita, A. Iwamatsu, T. Obinata, K. Ohashi, K. Mizuno, and S. Narumiya 1999. Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Science 285:895-8.
Maitra, N., I.L. Flink, J.J. Bahl, and E. Morkin. 2000. Expression of alpha and beta integrins during terminal differentiation of cardiomyocytes. Cardiovasc Res. 47:715-25.
Melendez, J., S. Welch, E. Schaefer, C.S. Moravec, S. Avraham, H. Avraham, and M.A. Sussman. 2002. Activation of pyk2/related focal adhesion tyrosine kinase and focal adhesion kinase in cardiac remodeling. J Biol Chem. 277:45203-10.
Miura, I., H. Hashizume, H. Akutsu, Y. Hara, and Y. Abiko. 1987. Accumulation of nonesterified fatty acids in the dog myocardium during coronary artery occlusion determined by a method using 9-anthryldiazomethane. Heart Vessels. 3:190-4.
Myrmel, T., K. Forsdahl, and T.S. Larsen. 1992. Triacylglycerol metabolism in hypoxic, glucose-deprived rat cardiomyocytes. J Mol Cell Cardiol. 24:855-68.
Nielsen, L.B., E.D. Bartels, and E. Bollano. 2002. Overexpression of apolipoprotein B in the heart impedes cardiac triglyceride accumulation and development of cardiac dysfunction in diabetic mice. J Biol Chem. 277:27014-20.
Oe, H., T. Kuzuya, S. Hoshida, M. Nishida, M. Hori, T. Kamada, and M. Tada. 1994. Calcium overload and cardiac myocyte cell damage induced by arachidonate lipoxygenation. Am J Physiol. 267:H1396-402.
Riemersma, R.A. 1987. Raised plasma non-esterified fatty acids (NEFA) during ischaemia: implications for arrhythmias. Basic Res Cardiol. 82 Suppl 1:177-86.
Sastry, S.K., P.D. Lyons, M.D. Schaller, and K. Burridge. 2002. PTP-PEST controls motility through regulation of Rac1. J Cell Sci. 115:4305-16.
Sastry S.K, Z. Rajfur, B.P. Liu, J.F. Cote, M.L. Tremblay,and K. Burridge. 2006. PTP-PEST couples membrane protrusion and tail retraction via VAV2 and p190RhoGAP. J Biol Chem. 281:11627-36.
Schaller, M.D. 2001. Biochemical signals and biological responses elicited by the focal adhesion kinase. Biochim Biophys Acta. 1540:1-21.
Schaller, M.D., J.D. Hildebrand, J.D. Shannon, J.W. Fox, R.R. Vines, and J.T. Parsons. 1994. Autophosphorylation of the focal adhesion kinase, pp125FAK, directs SH2-dependent binding of pp60src. Mol Cell Biol. 14:1680-8.
Schaller, M.D., and J.T. Parsons. 1995. pp125FAK-dependent tyrosine phosphorylation of paxillin creates a high-affinity binding site for Crk. Mol Cell Biol. 15:2635-45.
Sharp, W.W., D.G. Simpson, T.K. Borg, A.M. Samarel, and L. Terracio. 1997. Mechanical forces regulate focal adhesion and costamere assembly in cardiac myocytes. Am J Physiol. 273:H546-56.
Shen, Y., G. Schneider, J.F. Cloutier, A. Veillette, and M.D. Schaller. 1998. Direct association of protein-tyrosine phosphatase PTP-PEST with paxillin. J Biol Chem. 273:6474-81.
Sonnenberg, A. 1993. Integrins and their ligands. Curr Top Microbiol Immunol. 184:7-35.
Tamura, M., J. Gu, T. Takino, and K.M. Yamada. 1999. Tumor suppressor PTEN inhibition of cell invasion, migration, and growth: differential involvement of focal adhesion kinase and p130Cas. Cancer Res. 59:442-9.
Terracio, L., D.G. Simpson, L. Hilenski, W. Carver, R.S. Decker, N. Vinson, and T.K. Borg. 1990. Distribution of vinculin in the Z-disk of striated muscle: analysis by laser scanning confocal microscopy. J Cell Physiol. 145:78-87.
Thomas, J.W., M.A. Cooley, J.M. Broome, R. Salgia, J.D. Griffin, C.R. Lombardo, and M.D. Schaller. 1999. The role of focal adhesion kinase binding in the regulation of tyrosine phosphorylation of paxillin. J Biol Chem. 274:36684-92.
Tokuyasu, K.T. 1989. Immunocytochemical studies of cardiac myofibrillogenesis in early chick embryos. III. Generation of fasciae adherentes and costameres. J Cell Biol. 108:43-53.
Tomita, T., L. Wilson, and M. Chiga. 1990. Idiopathic dilated cardiomyopathy--an evidence of abnormal lipid accumulation accumulation in myocardium. Am J Cardiovasc Pathol. 3:81-5.
van der Flier, A., A.C. Gaspar, S. Thorsteinsdottir, C. Baudoin, E. Groeneveld, C.L. Mummery, and A. Sonnenberg. 1997. Spatial and temporal expression of the beta1D integrin during mouse development. Dev Dyn. 210:472-86.
van der Flier, A., I. Kuikman, C. Baudoin, R. van der Neut, and A. Sonnenberg. 1995. A novel beta 1 integrin isoform produced by alternative splicing: unique expression in cardiac and skeletal muscle. FEBS Lett. 369:340-4.
Wang SM, Y.J. Tsai, M.J. Jiang, and Y.Z. Tseng 1997. Studies on the function of rho A protein in cardiac myofibrillogenesis. J Cell Biochem. 66:43-53.
Young, M.E., P.H. Guthrie, P. Razeghi, B. Leighton, S. Abbasi, S. Patil, K.A. Youker, and H. Taegtmeyer. 2002. Impaired long-chain fatty acid oxidation and contractile dysfunction in the obese Zucker rat heart. Diabetes. 51:2587-95.
Zhidkova, N.I., A.M. Belkin, and R. Mayne. 1995. Novel isoform of beta 1 integrin expressed in skeletal and cardiac muscle. Biochem Biophys Res Commun. 214:279-85.


Dudnakova, T.V., O.V. Stepanova, K.V. Dergilev, A.V. Chadin, B.V. Shekhonin, D.M. Watterson, and V.P. Shirinsky. 2006. Myosin light chain kinase colocalizes with nonmuscle myosin IIB in myofibril precursors and sarcomeric Z-lines of cardiomyocytes. Cell Motil Cytoskeleton. 63:375-83.
Kimura, K., M. Ito, M. Amano, K. Chihara, Y. Fukata, M. Nakafuku, B. Yamamori, J. Feng, T. Nakano, K. Okawa, A. Iwamatsu, and K. Kaibuchi. 1996. Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase). Science. 273: 245-8.
Palmer, B.M. 2005. Thick filament proteins and performance in human heart failure. Heart Fail Rev. 10:187-97.
Pang, H., and K.N. Bitar. 2005. Direct association of RhoA with specific domains of PKC-alpha. Am J Physiol Cell Physiol. 289:C982-93.
Sastry, S.K., Z. Rajfur, B.P. Liu, J.F. Cote, M.L. Tremblay, and K. Burridge. 2006. PTP-PEST couples membrane protrusion and tail retraction via VAV2 and p190RhoGAP. J Biol Chem. 281:11627-36.
van Der Velden, J., L.J. Klein, R. Zaremba, N.M. Boontje, M.A. Huybregts, W. Stooker, L. Eijsman, J.W. de Jong, C.A. Visser, F.C. Visser, and G.J. Stienen. 2001. Effects of calcium, inorganic phosphate, and pH on isometric force in single skinned cardiomyocytes from donor and failing human hearts. Circulation. 104:1140-6.
van der Velden, J., Z. Papp, R. Zaremba, N.M. Boontje, J.W. de Jong, V.J. Owen, P.B. Burton, P. Goldmann, K. Jaquet, and G.J. Stienen. 2003. Increased Ca2+-sensitivity of the contractile apparatus in end-stage human heart failure results from altered phosphorylation of contractile proteins. Cardiovasc Res. 57:37-47.
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