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Dilated cardiomyopathy-linked heat shock protein family D member 1 mutations cause up-regulation of reactive oxygen species and autophagy through mitochondrial dysfunction (本文)

榎本, 博一 慶應義塾大学

2021.03.08

概要

Aims
During heart failure, the levels of circulatory heat shock protein family D member 1 (HSP60) increase. However, its underlying mechanism is still unknown. The apical domain of heat shock protein family D member 1 (HSPD1) is conserved throughout evolution. We found a point mutation in HSPD1 in a familial dilated cardiomyopathy (DCM) patient. A similar point mutation in HSPD1 in the zebrafish mutant, nbl, led to loss of its regenerative capacity and development of pericardial oedema under heat stress condition. In this study, we aimed to determine the direct in-volvement of HSPD1 in the development of DCM.

Methods and results
By Sanger method, we found a point mutation (Thr320Ala) in the apical domain of HSPD1, in one familial DCM pa- tient, which was four amino acids away from the point mutation (Val324Glu) in the nbl mutant zebrafish. The nbl mutants showed atrio-ventricular block and sudden death at 8-month post-fertilization. Histological and micro- scopic analysis of the nbl mutant hearts showed decreased ventricular wall thickness, elevated level of reactive oxy- gen species (ROS), increased fibrosis, mitochondrial damage, and increased autophagosomes. mRNA and protein expression of autophagy-related genes significantly increased in nbl mutants. We established HEK293 stable cell lines of wild-type, nbl-type, and DCM-type HSPD1, with tetracycline-dependent expression. Compared to wild-type, both nbl- and DCM-type cells showed decreased cell growth, increased expression of ROS and autophagy-related genes, inhibition of the activity of mitochondrial electron transport chain complexes III and IV, and decreased mito-chondrial fission and fusion.

Conclusion
Mutations in HSPD1 caused mitochondrial dysfunction and induced mitophagy. Mitochondrial dysfunction caused in- creased ROS and cardiac atrophy.

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参考文献

1. Schaper J, Froede R, Hein S, Buck A, Hashizume H, Speiser B, Friedl A, Bleese N. Impairment of the myocardial ultrastructure and changes of the cytoskeleton in di- lated cardiomyopathy. Circulation 1991;83:504–514.

2. Kimura A. Contribution of genetic factors to the pathogenesis of dilated cardiomyop-athy: the cause of dilated cardiomyopathy: genetic or acquired? (genetic-side). Circ J 2011;75:1756–1765.

3. Yoshikawa T. Contribution of acquired factors to the pathogenesis of dilated cardio- myopathy: the cause of dilated cardiomyopathy: genetic or acquired? (acquired-side). Circ J 2011;75:1766–1773.

4. Vogel B, Meder B, Just S, Laufer C, Berger I, Weber W, Katus HA, Rottbauer W. In-vivo characterization of human dilated cardiomyopathy genes in zebrafish. Biochem Biophys Res Commun 2009;390:516–522.

5. Kimura A. Molecular genetics and pathogenesis of cardiomyopathy. J Hum Genet 2016;61:41–50.

6. Lakdawala NK, Givertz MM. Dilated cardiomyopathy with conduction disease and ar- rhythmia. Circulation 2010;122:527–534.

7. Keller H, Finsterer J, Steger C, Wexberg P, Gatterer E, Khazen C, Stix G, Gerull B, Ho¨ ftberger R, Weidinger F. Novel c.367_369del LMNA mutation manifesting as se- vere arrhythmias, dilated cardiomyopathy, and myopathy. Heart Lung 2012;41: 382–386.

8. Lin KM, Lin B, Lian IY, Mestril R, Scheffler IE, Dillmann WH. Combined and individual mitochondrial HSP60 and HSP10 expression in cardiac myocytes protects mitochon- drial function and prevents apoptotic cell deaths induced by simulated ischemia-reox- ygenation. Circulation 2001;103:1787–1792.

9. Tang H, Chen Y, Liu X, Wang S, Lv Y, Wu D, Wang Q, Luo M, Deng H. Downregulation of HSP60 disrupts mitochondrial proteostasis to promote tumori- genesis and progression in clear cell renal cell carcinoma. Oncotarget 2016;7: 38822–38388.

10. Magnoni R, Palmfeldt J, Christensen JH, Sand M, Maltecca F, Corydon TJ, West M, Casari G, Bross P. Late onset motoneuron disorder caused by mitochondrial HSP60 chaperone deficiency in mice. Neurobiol Dis 2013;54:12–23.

11. Magen D, Georgopoulos C, Bross P, Ang D, Segev Y, Goldsher D, Nemirovski A, Shahar E, Ravid S, Luder A, Heno B, Gershoni-Baruch R, Skorecki K, Mandel H. Mitochondrial HSP60 chaperonopathy causes an autosomal-recessive neurodegener- ative disorder linked to brain hypomyelination and leukodystrophy. Am J Hum Genet 2008;83:30–42.

12. Sidorik L, Kyyamova R, Bobyk V, Kapustian L, Rozhko O, Vigontina O, Ryabenko D, Danko I, Maksymchuk O, Kovalenko VN, Filonenko VV, Chaschin NA. Molecular chaperone, HSP60, and cytochrome P450 2E1 co-expression in dilated cardiomyopa- thy. Cell Bio Int 2005;29:51–55.

13. Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, Yokoyama M, Mishima K, Saito I, Okano H, Mizushima N. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 2006;441: 885–889.

14. Chen MC, Chang JP, Wang YH, Liu WH, Ho WC, Chang HW. Autophagy as a mech- anism for myolysis of cardiomyocytes in mitral regurgitation. Eur J Clin Invest 2011;41: 299–307.

15. Wang L, Hao H, Wang J, Wang X, Zhang S, Du Y, Lv T, Zuo L, Li Y, Liu H. Decreased autophagy: a major factor for cardiomyocyte death induced by b1-adre- noceptor autoantibodies. Cell Death Dis 2015;6:e1862.

16. Nishida K, Kyoi S, Yamaguchi O, Sadoshima J, Otsu K. The role of autophagy in the heart. Cell Death Differ 2009;16:31–38.

17. Kubli DA, Gustafsson A˚ B. Mitochondria and mitophagy: the yin and yang of cell death control. Circ Res 2012;111:1208–1207.

18. Narendra D, Tanaka A, Suen DF, Youle RJ. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 2008;183:795–803.

19. Makino S, Whitehead GGc, Lien CL, Kim S, Jhawar P, Kono A, Kawata Y, Keating MT. Heat-shock protein 60 is required for blastema formation and maintenance dur- ing regeneration. Proc Natl Acad Sci U S A 2005;102:14599–14604.

20. Arimura T, Takeya R, Ishikawa T, Yamano T, Matsuo A, Tatsumi T, Nomura T, Sumimoto H, Kimura A. Dilated cardiomyopathy-associated FHOD3 variant impairs the ability to induce activation of transcription factor serum response factor. Circ J 2013;77:2990–2996.

21. Adisa AO, Udeabor SE, Kubesch A, Barbeck M, Ghanaati S. The utility of azan tri- chrome staining in ameloblastoma. Niger Postgrad Med J 2016;23:44–46.

22. Kanda Y. Investigation of the freely-available easy-to-use software “EZR” (Easy R) for medical statistics. Bone Marrow Transplant 2013;48:452–458.

23. Kabeya Y, Mizushima N, Ueno T. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 2000;19: 5720–5728.

24. Radford SE. GroEL: more than just a folding cage. Cell 2006;125:831–833.

25. Kim KH, Song K, Yoon SH, Shehzad O, Kim YS, Son JH. Rescue of PINK1 null-specific mitochondrial complex IV deficits By ginsenoside Re activation of nitric oxide signaling. J Biol Chem 2012;287:44109–44120.

26. Kaufman BA, Kolesar JE, Perlman PS, Butow RA. A function for the mitochondrial chaperonin HSP60 in the structure and transmission of mitochondrial DNA nucle-oids in Saccharomyces cerevisiae. J Cell Biol 2003;163:457–461.

27. Barone R, Macaluso F, Sangiorgi C, Campanella C, Marino Gammazza A, Moresi V, Coletti D, Conway de Macario E, Macario AJ, Cappello F, Adamo S, Farina F, Zummo G, Di Felice V. Skeletal muscle Heat shock protein 60 increases after endur-ance training and induces peroxisome proliferator-activated receptor gamma coacti-vator 1 a1 expression. Sci Rep 2016;6:19781.

28. Noelker C, Morel L, Osterloh A, Alvarez-Fischer D, Lescot T, Breloer M, Gold M, Oertel WH, Henze C, Michel PP, Dodel RC, Lu L, Hirsch EC, Hunot S, Hartmann A. Heat shock protein 60: an endogenous inducer of dopaminergic cell death in Parkinson disease. J Neuroinflammation 2014;11:86–98.

29. Norton N, Li D, Rieder MJ, Siegfried JD, Rampersaud E, Zu¨chner S, Mangos S, Gonzalez-Quintana J, Wang L, McGee S, Reiser J, Martin E, Nickerson DA, Hershberger RE. Genome-wide studies of copy number variation and exome se-quencing identify rare variants in BAG3 as a cause of dilated cardiomyopathy. Am J Hum Genet 2011;88:273–282.

30. Pluess M, Daeubler G, Dos Remedios CG, Ehler E. Adaptations of cytoarchitecture in human dilated cardiomyopathy. Biophys Rev 2015;7:25–32.

31. Kreutmayer SB, Messner B, Knoflach M, Henderson B, Niederegger H, Bo¨ ck G, Van der Zee R, Wick G, Bernhard D. Dynamics of heat shock protein 60 in endothelial cells exposed to cigarette smoke extract. J Mol Cell Cardiol 2011;51:777–780.

32. Kao TY, Chiu YC, Fang WC, Cheng CW, Kuo CY, Juan HF, Wu SH, Lee AY. Mitochondrial Lon regulates apoptosis through the association with Hsp60-mtHsp70 complex. Cell Death Dis 2015;6:e1642.

33. Chen Y, Liu Y, Dorn GW II. Mitochondrial fusion is essential for organelle function and cardiac homeostasis. Circ Res 2011;109:1327–1331.

34. Chen Y, Dorn GW II. PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. Science 2013;340:471–475.

35. Lesnefsky EJ, Chen Q, Hoppel CL. Mitochondrial metabolism in aging heart. Circ Res 2016;118:1593–1611.

36. Youle RJ, and, Narendra DP. Mechanisms of mitophagy. Nat Rev Mol Cell Biol 2011; 12:9–13.

37. Eisenberg-Lerner A, Kimchi A. The paradox of autophagy and its implication in can-cer etiology and therapy. Apoptosis 2009;14:376–391.

38. Cao DJ, Jiang N, Blagg A, Johnstone JL, Gondalia R, Oh M, Luo X, Yang KC, Shelton JM, Rothermel BA, Gillette TG, Dorn GW, Hill JA. Mechanical unloading activates FoxO3 to trigger Bnip3-dependent cardiomyocyte atrophy. J Am Heart Assoc 2013;2: e000016.

39. Attaix D, Bechet D. FoxO3 controls dangerous proteolytic liaisons. Cell Metab 2007; 6:425–427.

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