臺灣博碩士論文加值系統

廣東住血線蟲，大鼠肺屬線蟲，是嗜酸性腦膜炎的主要病因。大鼠為是此線蟲的終宿主。人類也可因誤食第三期幼蟲導致嗜酸性腦膜炎感染。典型的臨床表現是急性腦膜炎與嗜酸性白血球增多。粒線體動力平衡是細胞穩定動態調節重要關鍵。本研究探討廣東住血線蟲感染對小鼠腦組織細胞、粒線體形態、動力學和功能的的直接影響。使用25隻廣東住血線蟲第三期幼蟲感染小鼠，共分5組（正常與感染後1-4週，每組各五隻小鼠）。使用穿透式電子顯微鏡可觀察感染廣東住血線蟲腦組織之粒線體呈現分裂情形，且感染第三週的腦細胞嚴重受損，粒線體呈現空洞萎縮化。西方墨點法結果可發現粒線體相關之分裂（Fission）、生合成（biogenesis）及自 噬（Mitophagy），且 蛋白皆在感染後第二、三週有明顯的上升的趨勢。粒線體融合（Fusion）蛋白則是在第二、三週呈現下降的趨勢及粒線體抗細胞凋亡（Anti-apoptosis） 蛋白（caspase 8及9）感染後第二、三週有明顯的上升。在腦組織切片，可發現感染後的小鼠腦膜出現發炎與破損，且幼蟲滲透到大腦皮層和幼蟲周圍有細胞浸潤現象。在TUNEL試驗，感染第二週小鼠腦組織切片的細胞凋亡細胞量呈上升的趨勢，第三、四週因感染過於嚴重導致腦細胞壞死。Annexin V的實驗可發現感染後小鼠腦細胞壞死情形也呈上升的趨勢。粒線體之功能方面，可確認粒線體膜電位在感染後有呈上升的趨勢，到第四週則下降，可能是因細胞壞死導致無法偵測到膜電位。本研究證實感染廣東住血線蟲會造成小鼠腦部組織之粒線體的整體變化並顯示出粒線體分裂、融合、生合成、自噬與凋亡皆受到影響，最後導致粒線體動態平衡受到破壞。

Angiostrongylus cantonensis, the rat lungworm, is the major cause of eosinophilic meningitis. Rats are the definitive host of this nematode. Human can be infected by eating the third larvae from intermediate hosts. The symptoms of eosinophilic meningitis are meningitis and eosinophilic pleocytosis. Mitochondrial dynamic is crucial for the regulation of cell homeostasis. In this study, we attempted to assess the direct effects of A. cantonensis infection on mice brain, and to explore the expression of mitochondrial morphology, dynamics, and function. There were 5 groups (normal and 1, 2, 3 and 4 week post infection) of mice (5 mice in each group and each mice was infected with 25 L3 of A. cantonensis). Fission of mitochondria can be observed by TEM (transmission electronic microscopy). The brain cells were severely damaged and the mitochondria of showed atrophy at third week post infection. By western blotting, the protein of mitochondrial fission, biogenesis and mitophagy was increased, and the fussion protein was decreased at second and third week post infection. The protein of apoptosis (caspase 8 and 9) had significant increasd. Tthe mouse meningeal after infection can be found inflammation and damage in the sections of the brain tissue. Larvae were embedded in the cortex, and cell infiltration could be found around larvae. In TUNEL assay, the number of apoptotic cells was increased in the mice brain at second week post infection, and brain cell necrosis was more serious at third and fourth week post infection. It was also found that brain cell necrosis was increased in infected mice by Annexin V test. For mitochondrial function, membrane potential was detected. It was increased after infection, but it could not be detected at fourth week post infection. This may due to cell necrosis and therefore membrane potential could not be detected. These results confirmed that the A. cantonensis infection can influence mitochondrial dynamic, biogenesis, morphology and function in mice model.

中文摘要 I
英文摘要 II
目錄 IV
表目錄 VIII圖目錄 IX
附錄 XIII第一章 研究背景及目的（Introduction） 1
一、廣東住血線蟲病 1
二、廣東住血線蟲 1
三、廣東住血線蟲生活史 2
四、感染廣東住血線蟲之臨床病徵 3
五、廣東住血線蟲之診斷 4
六、廣東住血線蟲之防治 4
七、粒線體動力學 5
八、粒線體之融合與分裂交互作用 5
九、粒線體之自噬作用 6
十、粒線體之生合成 7
十一、粒線體之凋亡與壞死 7
十二、前人相關研究 9
十三、研究目的 11
第二章 研究材料及方法（Materials and Methods） 12
一、廣東住血線蟲生活史之維持 12
1.實驗室實驗動物與中間宿主 12
2.第一期幼蟲(First-stage larva)之收集 12
3.第三期幼蟲(Third-stage larva)之收集與感染SD實驗大鼠維持生活史 12
4.第三期廣東住血線蟲幼蟲感染BALB/C實驗小鼠 13
二、從腦組織中抽RNA 13
三、反轉錄聚合脢反應(互補去氧核糖核酸（cDNA）之合成) 14
四、定量聚合酶連鎖反應Real-time PCR 14
五、腦組織soluble protein之萃取 14
六、蛋白質定量 15
七、膠體電泳分離 15
八、西方墨點法 16
九、石蠟切片之H&E Staining 17
十、TUNEL螢光切片染色 19
十一、穿透式電子顯微鏡(TEM) 20
十二、Annexin Ⅴ-FITC/PI 雙重染色 20
十三、JC-1 粒線體膜電位染色 21
十四、統計分析 22
第三章 結果（Results） 23
一、小鼠感染廣東住血線蟲之病變 23
二、小鼠腦組織Hematoxylin & Eosin stain病理變化之分析 23
三、正常未感染與感染後小鼠腦組織切片比較 24
四、正常未感染與感染後小鼠腦組織穿透式電子顯微鏡比較 24
五、使用Flow cytometry分析小鼠腦組織粒線體膜電位變化 24
六、小鼠腦組織中與粒線體相關mRNA之分析 24
1.β-actin mRNA測定 25
2.粒線體分裂(Fission)基因mRNA分析:Fis-1 and Drp-1表現 25
3.粒線體融合(Fusion)基因mRNA分析：Mfn-2、mMfn-1 and Opa-1表現 25
4.粒線體生合成(Biogenesis)基因mRNA分析：Tfam表現 25
5.粒線體抗細胞凋亡(Anti-apoptosis) 基因mRNA分析：Bcl-2、 Bcl-xL and Mcl-1表現 25
6.粒線體自噬(Mitophagy) 基因mRNA分析：Beclin-1、Pink、p62 and Nix mRNA表現 26
七、小鼠腦組織中與粒線體相關蛋白分析 26
1.粒線體分裂(Fission)蛋白之Fis-1表現 26
2.粒線體分裂(Fission)蛋白之Drp-1 (S616)表現 26
3.粒線體分裂(Fission)蛋白之Drp-1 (total)表現 26
4.粒線體融合(Fusion)蛋白之Mfn-2表現 27
5.粒線體融合(Fusion)蛋白之Opa-1表現 27
6.粒線體融合(Fusion)蛋白之Drp-1(s637)表現 27
7.粒線體生合成(Biogenesis)蛋白之PGC1-α表現 27
8.粒線體生合成(Biogenesis)蛋白之Tfam之表現 27
9.粒線體細胞凋亡(Apoptosis)蛋白之caspase-8表現 28
10.粒線體細胞凋亡(Apoptosis)蛋白之caspase-9表現 28
11.粒線體細胞凋亡(Apoptosis)蛋白之caspase-3表現 28
八、以TUNEL assay分析小鼠腦組織切片 28
九、Flow cytometry分析小鼠腦組織壞死的細胞(necrosis cell) 29
1.以Flow cytometry分析正常未感染與感染之小鼠腦組織nercosis細胞表現 29
2.以Flow cytometry分析正常未感染與感染之小鼠腦組織late apoptosis細胞表現 29
3.以Flow cytometry分析正常未感染與感染之小鼠腦組織early apoptosis細胞表現 29
十、小鼠感染廣東住血線蟲後腦細胞之粒線體動態變化路徑 29
第四章 討論（Discussion） 31
第五章 參考文獻（Reference） 36



表目錄
表一Primer pairs for candidate genes used in real time PCR. 42

圖目錄
圖一：廣東住血線蟲各時期之糞檢與中間宿主。 44
圖二：正常未感染與感染廣東住血線蟲第一週小鼠腦組織切片比較。 45
圖三：正常未感染與感染廣東住血線蟲第二週小鼠腦組織切片比較。 46
圖四：正常未感染與感染廣東住血線蟲第三週小鼠腦組織切片比較。 47
圖五：正常未感染與感染廣東住血線蟲第四週小鼠腦組織切片比較。 48
圖六：使用電子顯微鏡(TEM)觀察正常未感染與感染廣東住血線蟲小鼠腦組織，比較粒線體型態。 49
圖七：使用穿透電子顯微鏡(TEM)觀察正常未感染與感染廣東住血線蟲小鼠腦組織，比較粒線體數目變化。 50
圖八：以Flow cytometry分析正常與感染廣東住血線蟲後第一週與第二週之腦組織粒線體膜電位差異。 51
圖九：以Flow cytometry分析正常與感染廣東住血線蟲後第三週與第四週之腦組織粒線體膜電位差異。 52
圖十：以Flow cytometry分析正常與感染廣東住血線蟲後不同週數(感染後第1、2、3、4週)之腦組織粒線體膜電位差異。 53
圖十一：以qRT-PCR分析正常與感染廣東住血線蟲後不同週數(感染後第1、2、3、4週)之腦組織Mitochondrial fission mRNA表現。 54
圖十二：以qRT-PCR分析正常與感染廣東住血線蟲後不同週數(感染後第1、2、3、4週)之腦組織Mitochondrial fusion mRNA表現。 55
圖十三：以qRT-PCR分析正常與感染廣東住血線蟲後不同週數(感染後第1、2、3、4週)之腦組織Mitochondrial biogenesis mRNA表現。 56
圖十四：以qRT-PCR分析正常與感染廣東住血線蟲後不同週數(感染後第1、2、3、4週)之腦組織Mitochondrial anti-apoptosis mRNA表現。 57
圖十五：以qRT-PCR分析正常與感染廣東住血線蟲後不同週數(感染後第1、2、3、4週)之腦組織Mitochondrial mitophagy mRNA表現。 58
圖十六：以Western blot分析正常與感染廣東住血線蟲後不同週數(感染後第1、2、3、4週)之腦組織Fis-1 (Mitochondrial fission) 蛋白表現。 59
圖十七：以Western blot分析正常與感染廣東住血線蟲後不同週數(感染後第1、2、3、4週)之腦組織Drp-1(S616) (Mitochondrial fission) 蛋白表現。 60
圖十八：以Western blot分析正常與感染廣東住血線蟲後不同週數(感染後第1、2、3、4週)之腦組織Total Drp-1 (Mitochondrial fission) 蛋白表現。 61
圖十九：以Western blot分析正常與感染廣東住血線蟲後不同週數(感染後第1、2、3、4週)之腦組織Mfn-2 (Mitochondrial fussion) 蛋白表現。 62
圖二十：以Western blot分析正常與感染廣東住血線蟲後不同週數(感染後第1、2、3、4週)之腦組織Opa-1 (Mitochondrial fussion)蛋白表現。 63
圖二十一：以Western blot分析正常與感染廣東住血線蟲後不同週數(感染後第1、2、3、4週)之腦組織Drp-1(S637) (Mitochondrial fussion)蛋白表現。 64
圖二十二：以Western blot分析正常與感染廣東住血線蟲後不同週數(感染後第1、2、3、4週)之腦組織PGC1-α (Mitochondrial biogenesis)蛋白表現。 65
圖二十三：以Western blot分析正常與感染廣東住血線蟲後不同週數(感染後第1、2、3、4週)之腦組織Tfam (Mitochondrial biogenesis)蛋白表現。 66
圖二十四：以Western blot分析正常與感染廣東住血線蟲後不同週數(感染後第1、2、3、4週)之腦組織caspase-8 (Mitochondrial anti-apoptosis)蛋白表現。 67
圖二十五：以Western blot分析正常與感染廣東住血線蟲後不同週數(感染後第1、2、3、4週)之腦組織caspase-9 (Mitochondrial anti-apoptosis)蛋白表現。 68
圖二十六：以Western blot分析正常與感染廣東住血線蟲後不同週數(感染後第1、2、3、4週)之腦組織caspase-3 (Mitochondrial anti-apoptosis)蛋白表現。 69
圖二十七：以TUNEL assay分析正常未感染小鼠之腦組織apoptosis細胞表現。 70
圖二十八：以TUNEL assay分析感染廣東住血線蟲第一週小鼠之腦組織apoptosis細胞表現。 71
圖二十九：以TUNEL assay分析感染廣東住血線蟲第二週小鼠之腦組織apoptosis細胞表現。 72
圖三十：以TUNEL assay分析感染廣東住血線蟲第三週小鼠之腦組織apoptosis細胞表現。 73
圖三十一：以TUNEL assay分析感染廣東住血線蟲第四週小鼠之腦組織apoptosis細胞表現。 74
圖三十二：以TUNEL assay分析正常與感染廣東住血線蟲後不同週數(感染後第1、2、3、4週)之腦組織apoptosis細胞表現差異。 75
圖三十三：以Flow cytometry分析正常與感染廣東住血線蟲後不同週數(感染後第1、2、3、4週)之腦組織細胞表現。 76
圖三十四：以Flow cytometry分析正常與感染廣東住血線蟲後不同週數(感染後第1、2、3、4週)之腦組織necrosis細胞表現。 77
圖三十五：以Flow cytometry分析正常與感染廣東住血線蟲後不同週數(感染後第1、2、3、4週)之腦組織late apoptosis細胞表現。 78
圖三十六：以Flow cytometry分析正常與感染廣東住血線蟲後不同週數(感染後第1、2、3、4週)之腦組織early apoptosis細胞表現。 79
圖三十七：小鼠感染廣東住血線蟲後腦細胞之粒線體動態變化路徑。(前期：第一週到第三週) 80
圖三十八：小鼠感染廣東住血線蟲後腦細胞之粒線體動態變化路徑。(後期：第四週) 81


附錄
圖一：粒線體之動態平衡。 82
圖二：細胞凋亡機轉。 83

Alicata, J.E. (1988). Angiostrongylus cantonensis and eosinophilic meningitis. Journal of Washington Academy science 78, 38-46.
Alicata, J.E., and Brown, R.W. (1962). OBSERVATIONS ON THE METHOD OF HUMAN INFECTION WITH ANGIOSTRONGYLUS CANTONENSIS IN TAHITI. Canadian Journal of Zoology 40, 755-760.
Anderson, C.A., and Blackstone, C. (2013). SUMO wrestling with Drp1 at mitochondria. The EMBO journal 32, 1496-1498.
Apostolova, N., Gomez-Sucerquia, L.J., Gortat, A., Blas-Garcia, A., and Esplugues, J.V. (2011). Autophagy as a rescue mechanism in efavirenz-induced mitochondrial dysfunction: a lesson from hepatic cells. Autophagy 7, 1402-1404.
Beaver, P.C., and Rosen, L. (1964). MEMORANDUM ON THE FIRST REPORT OF ANGIOSTRONGYLUS IN MAN, BY NOMURA AND LIN, 1945. The American journal of tropical medicine and hygiene 13, 589-590.
Beurg, M., Hafidi, A., Skinner, L., Cowan, G., Hondarrague, Y., Mitchell, T.J., and Dulon, D. (2005). The mechanism of pneumolysin-induced cochlear hair cell death in the rat. The Journal of physiology 568, 211-227.
Braun, J.S., Hoffmann, O., Schickhaus, M., Freyer, D., Dagand, E., Bermpohl, D., Mitchell, T.J., Bechmann, I., and Weber, J.R. (2007). Pneumolysin causes neuronal cell death through mitochondrial damage. Infection and Immunity 75, 4245-4254.
Braun, J.S., Sublett, J.E., Freyer, D., Mitchell, T.J., Cleveland, J.L., Tuomanen, E.I., and Weber, J.R. (2002). Pneumococcal pneumolysin and H(2)O(2) mediate brain cell apoptosis during meningitis. The Journal of clinical investigation 109, 19-27.
Cai, Q., and Tammineni, P. (2016). Alterations in Mitochondrial Quality Control in Alzheimer’s Disease. Frontiers in Cellular Neuroscience 10.
Canto, C., and Auwerx, J. (2009). PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Current opinion in lipidology 20, 98-105.
Chan, D.C. (2012). Fusion and fission: interlinked processes critical for mitochondrial health. Annual review of genetics 46, 265-287.
Chan, F.K., Moriwaki, K., and De Rosa, M.J. (2013). Detection of necrosis by release of lactate dehydrogenase activity. Methods in molecular biology (Clifton, NJ) 979, 65-70.
Chang, C.R., and Blackstone, C. (2010). Dynamic regulation of mitochondrial fission through modification of the dynamin-related protein Drp1. Annals of the New York Academy of Sciences 1201, 34-39.
Chen, H., Detmer, S.A., Ewald, A.J., Griffin, E.E., Fraser, S.E., and Chan, D.C. (2003). Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. The Journal of cell biology 160, 189-200.
Chen, T.T., Wu, L.S., Hsu, P.W., Pang, C.Y., Lee, K.M., Cheng, P.C., and Peng, S.Y. (2015). Mitochondrial dynamics in the mouse liver infected by Schistosoma mansoni. Acta tropica 148, 13-23.
Chen, Y., and Dorn, G.W., 2nd (2013). PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. Science (New York, NY) 340, 471-475.
Corrado, M., Scorrano, L., and Campello, S. (2012). Mitochondrial dynamics in cancer and neurodegenerative and neuroinflammatory diseases. International journal of cell biology 2012, 729290.
Danial, N.N., and Korsmeyer, S.J. (2004). Cell death: critical control points. Cell 116, 205-219.
Darwin, M.K.B.F. (2007). Food-Borne Parasitic Zoonoses, Vol 11 (New York: Springer).
Dorn, G.W., 2nd, and Kitsis, R.N. (2015). The mitochondrial dynamism-mitophagy-cell death interactome: multiple roles performed by members of a mitochondrial molecular ensemble. Circulation research 116, 167-182.
Du, C., Fang, M., Li, Y., Li, L., and Wang, X. (2000). Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 102, 33-42.
Eamsobhana, P. (2013). Angiostrongyliasis in Thailand: Epidemiology and Laboratory Investigations. Hawai'i Journal of Medicine & Public Health 72, 28-32.
Eamsobhana, P. (2014). Eosinophilic meningitis caused by Angiostrongylus cantonensis--a neglected disease with escalating importance. Tropical biomedicine 31, 569-578.
Eamsobhana, P., Wanachiwanawin, D., Dechkum, N., Parsartvit, A., and Yong, H.S. (2013). Molecular diagnosis of eosinophilic meningitis due to Angiostrongylus cantonensis (Nematoda: Metastrongyloidea) by polymerase chain reaction-DNA sequencing of cerebrospinal fluids of patients. Memórias do Instituto Oswaldo Cruz 108, 116-118.
Eamsobhana, P., and Yong, H.S. (2009). Immunological diagnosis of human angiostrongyliasis due to Angiostrongylus cantonensis (Nematoda: Angiostrongylidae). International Journal of Infectious Diseases 13, 425-431.
Feng, D., Liu, L., Zhu, Y., and Chen, Q. (2013). Molecular signaling toward mitophagy and its physiological significance. Experimental cell research 319, 1697-1705.
Frank, S., Gaume, B., Bergmann-Leitner, E.S., Leitner, W.W., Robert, E.G., Catez, F., Smith, C.L., and Youle, R.J. (2001). The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. Developmental cell 1, 515-525.
Gomes, L.C., Di Benedetto, G., and Scorrano, L. (2011). During autophagy mitochondria elongate, are spared from degradation and sustain cell viability. Nature cell biology 13, 589-598.
Gores, G.J., and Kaufmann, S.H. (2001). Is TRAIL hepatotoxic? Hepatology (Baltimore, Md) 34, 3-6.
Haanen, C., and Vermes, I. (1995). Apoptosis and inflammation. Mediators of Inflammation 4, 5-15.
Haanen, C., and Vermes, I. (1996). Apoptosis: programmed cell death in fetal development. European journal of obstetrics, gynecology, and reproductive biology 64, 129-133.
Hollyer, J.R. (2013). Telling Consumers, Gardeners, and Farmers about the Possible Risk of Rat Lungworm in the Local Food Supply in Hawai‘i (Hawaii J Med Public Health. 2013 Jun;72(6 Suppl 2):82.).
Hu, X., Li, J.-H., Lan, L., Wu, F.-F., Zhang, E.-P., Song, Z.-M., Huang, H.-C., Luo, F.-J., Pan, C.-W., and Tan, F. (2012). In Vitro Study of the Effects of Angiostrongylus cantonensis Larvae Extracts on Apoptosis and Dysfunction in the Blood-Brain Barrier (BBB). PLOS ONE 7, e32161.
Iqbal, S., and Hood, D.A. (2015). The role of mitochondrial fusion and fission in skeletal muscle function and dysfunction. Frontiers in bioscience (Landmark edition) 20, 157-172.
Jaroonvesama, N. (1988). Differential diagnosis of eosinophilic meningitis. Parasitology Today 4, 262-266.
Jheng, H.F., Tsai, P.J., Guo, S.M., Kuo, L.H., Chang, C.S., Su, I.J., Chang, C.R., and Tsai, Y.S. (2012). Mitochondrial fission contributes to mitochondrial dysfunction and insulin resistance in skeletal muscle. Molecular and cellular biology 32, 309-319.
Jin, S.M., Lazarou, M., Wang, C., Kane, L.A., Narendra, D.P., and Youle, R.J. (2010). Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL. The Journal of cell biology 191, 933-942.
Jin, S.M., and Youle, R.J. (2013). The accumulation of misfolded proteins in the mitochondrial matrix is sensed by PINK1 to induce PARK2/Parkin-mediated mitophagy of polarized mitochondria. Autophagy 9, 1750-1757.
Kang, D., Kim, S.H., and Hamasaki, N. (2007). Mitochondrial transcription factor A (TFAM): roles in maintenance of mtDNA and cellular functions. Mitochondrion 7, 39-44.
Kerr, J.F., Wyllie, A.H., and Currie, A.R. (1972). Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. British journal of cancer 26, 239-257.
Kim, K.W., Ha, K.Y., Lee, J.S., Rhyu, K.W., An, H.S., and Woo, Y.K. (2007). The apoptotic effects of oxidative stress and antiapoptotic effects of caspase inhibitors on rat notochordal cells. Spine 32, 2443-2448.
Kim, Y., Park, J., Kim, S., Song, S., Kwon, S.K., Lee, S.H., Kitada, T., Kim, J.M., and Chung, J. (2008). PINK1 controls mitochondrial localization of Parkin through direct phosphorylation. Biochemical and biophysical research communications 377, 975-980.
Kleinschmidt, M.C., Michaelis, M., Ogbomo, H., Doerr, H.-W., and Cinatl, J. (2007). Inhibition of apoptosis prevents West Nile virus induced cell death. BMC Microbiology 7, 49.
Kotiadis, V.N., Duchen, M.R., and Osellame, L.D. (2014a). Mitochondrial quality control and communications with the nucleus are important in maintaining mitochondrial function and cell health. Biochimica et Biophysica Acta (BBA) - General Subjects 1840, 1254-1265.
Kotiadis, V.N., Duchen, M.R., and Osellame, L.D. (2014b). Mitochondrial quality control and communications with the nucleus are important in maintaining mitochondrial function and cell health. Biochimica et biophysica acta 1840, 1254-1265.
Larsson, N.G., Wang, J., Wilhelmsson, H., Oldfors, A., Rustin, P., Lewandoski, M., Barsh, G.S., and Clayton, D.A. (1998). Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice. Nature genetics 18, 231-236.
Liesa, M., Palacin, M., and Zorzano, A. (2009). Mitochondrial dynamics in mammalian health and disease. Physiological reviews 89, 799-845.
Nemoto, S., Fergusson, M.M., and Finkel, T. (2005). SIRT1 functionally interacts with the metabolic regulator and transcriptional coactivator PGC-1{alpha}. The Journal of biological chemistry 280, 16456-16460.
Pop, C., and Salvesen, G.S. (2009). Human caspases: activation, specificity, and regulation. The Journal of biological chemistry 284, 21777-21781.
Rasbach, K.A., and Schnellmann, R.G. (2007). Signaling of mitochondrial biogenesis following oxidant injury. The Journal of biological chemistry 282, 2355-2362.
Rust, C., and Gores, G.J. (2000). Apoptosis and liver disease. The American journal of medicine 108, 567-574.
Sawanyawisuth, K., Kitthaweesin, K., Limpawattana, P., Intapan, P.M., Tiamkao, S., Jitpimolmard, S., and Chotmongkol, V. (2007). Intraocular angiostrongyliasis: clinical findings, treatments and outcomes. Transactions of the Royal Society of Tropical Medicine and Hygiene 101, 497-501.
Sawanyawisuth, K., and Sawanyawisuth, K. (2008). Treatment of angiostrongyliasis. Transactions of the Royal Society of Tropical Medicine and Hygiene 102, 990-996.
Sawanyawisuth, K., Takahashi, K., Hoshuyama, T., Sawanyawisuth, K., Senthong, V., Limpawattana, P., Intapan, P.M., Wilson, D., Tiamkao, S., Jitpimolmard, S., et al. (2009). Clinical factors predictive of encephalitis caused by Angiostrongylus cantonensis. The American journal of tropical medicine and hygiene 81, 698-701.
Smirnova, E., Griparic, L., Shurland, D.L., and van der Bliek, A.M. (2001). Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. Molecular biology of the cell 12, 2245-2256.
Spratt, D.M. (2015). Species of Angiostrongylus (Nematoda: Metastrongyloidea) in wildlife: A review. International journal for parasitology Parasites and wildlife 4, 178-189.
Stankov, M.V., Panayotova-Dimitrova, D., Leverkus, M., Vondran, F.W., Bauerfeind, R., Binz, A., and Behrens, G.M. (2012). Autophagy inhibition due to thymidine analogues as novel mechanism leading to hepatocyte dysfunction and lipid accumulation. AIDS (London, England) 26, 1995-2006.
Suliman, H.B., and Piantadosi, C.A. (2016). Mitochondrial Quality Control as a Therapeutic Target. Pharmacological reviews 68, 20-48.
Tsai, H.C., Lee, B.Y., Yen, C.M., Wann, S.R., Lee, S.S., and Chen, Y.S. (2015). Dexamethasone inhibits brain apoptosis in mice with eosinophilic meningitis caused by Angiostrongylus cantonensis infection. Parasites & vectors 8, 200.
Tsai, H.C., Liu, Y.C., Kunin, C.M., Lee, S.S., Chen, Y.S., Lin, H.H., Tsai, T.H., Lin, W.R., Huang, C.K., Yen, M.Y., et al. (2001). Eosinophilic meningitis caused by Angiostrongylus cantonensis: report of 17 cases. The American journal of medicine 111, 109-114.
Twig, G., Elorza, A., Molina, A.J., Mohamed, H., Wikstrom, J.D., Walzer, G., Stiles, L., Haigh, S.E., Katz, S., Las, G., et al. (2008). Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. The EMBO journal 27, 433-446.
Uchide, N., Ohyama, K., Bessho, T., and Toyoda, H. (2009). Lactate dehydrogenase leakage as a marker for apoptotic cell degradation induced by influenza virus infection in human fetal membrane cells. Intervirology 52, 164-173.
Van Laar, V.S., and Berman, S.B. (2013). The Interplay of Neuronal Mitochondrial Dynamics and Bioenergetics: Implications for Parkinson’s Disease. Neurobiology of disease 51, 43-55.
Vu, K., Eigenheer, R.A., Phinney, B.S., and Gelli, A. (2013). Cryptococcus neoformans Promotes Its Transmigration into the Central Nervous System by Inducing Molecular and Cellular Changes in Brain Endothelial Cells. Infection and Immunity 81, 3139-3147.
Wang, L.C., Jung, S.M., Chen, K.Y., Wang, T.Y., and Li, C.H. (2015). Temporal-spatial pathological changes in the brains of permissive and non-permissive hosts experimentally infected with Angiostrongylus cantonensis. Experimental parasitology 157, 177-184.
Wang, Q.-P., Lai, D.-H., Zhu, X.-Q., Chen, X.-G., and Lun, Z.-R. (2008). Human angiostrongyliasis. The Lancet Infectious Diseases 8, 621-630.
Wang, Q.P., Wu, Z.D., Wei, J., Owen, R.L., and Lun, Z.R. (2012). Human Angiostrongylus cantonensis: an update. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 31, 389-395.
Wang, X., Winter, D., Ashrafi, G., Schlehe, J., Wong, Y.L., Selkoe, D., Rice, S., Steen, J., LaVoie, M.J., and Schwarz, T.L. (2011). PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell 147, 893-906.
Wei, M.C., Zong, W.X., Cheng, E.H., Lindsten, T., Panoutsakopoulou, V., Ross, A.J., Roth, K.A., MacGregor, G.R., Thompson, C.B., and Korsmeyer, S.J. (2001). Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science (New York, NY) 292, 727-730.
Wu, Z., Puigserver, P., Andersson, U., Zhang, C., Adelmant, G., Mootha, V., Troy, A., Cinti, S., Lowell, B., Scarpulla, R.C., et al. (1999). Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98, 115-124.
Youle, R.J., and Strasser, A. (2008). The BCL-2 protein family: opposing activities that mediate cell death. Nature reviews Molecular cell biology 9, 47-59.
Youle, R.J., and van der Bliek, A.M. (2012). Mitochondrial fission, fusion, and stress. Science (New York, NY) 337, 1062-1065.