Role of VDAC1 in hepatocyte apoptosis during acute liver injury in rats induced by obstructive jaundice | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 11، دوره 28، شماره 1، فروردین 2025، صفحه 87-97 اصل مقاله (657.73 K) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2024.78454.16962 | ||
| نویسندگان | ||
| Jinshan Liu1، 2، 3؛ Jinlong Hu3؛ Hongyu Xu1، 2، 3؛ Liang Yan3، 4؛ Jiaming Yao* 3؛ Baoqiang Cao* 1، 2، 3 | ||
| 1Anhui No.2 Provincial People’s Hospital Clinical College of Anhui Medical University, Hefei 230041, Anhui, China | ||
| 2The Fifth Clinical Medical College of Anhui Medical University, Hefei 230041, Anhui, China | ||
| 3Anhui No.2 Provincial People’s Hospital, Hefei 230041, Anhui, China | ||
| 4Anhui University of Science & Technology, Huainan 232001, Anhui, China | ||
| چکیده | ||
| Objective(s): Exploring the role of VDAC1 in hepatocyte apoptosis during acute liver injury induced by obstructive jaundice. Materials and Methods: Animal and cell models were established to investigate possible mechanisms during acute liver injury induced by OJ. Blood was collected for liver function assessment. H&E and TEM were employed to observe pathological changes in the liver tissues. Flow cytometry was used to measure the hepatocyte apoptosis. The mitochondrial MPTP assay was employed to assess the mitochondrial function of hepatocytes. IHC, western blot, and qRT-PCR were employed to determine the expression levels of VDAC1. Then, VDAC-siRNA was used to establish a knockdown model. Flow cytometry was used again to measure hepatocyte apoptosis following VDAC1 knockdown. Results: The serum of rats in the OJ group exhibited a significant increase in liver function. Irregular tissue structure and mitochondrial morphology were observed in the liver tissues of OJ rats. A significant increase in mitochondrial permeability in hepatocytes. The expression levels of VDAC1 were significantly increased in the liver tissue of OJ rats. They were also significantly increased in the hepatocytes, primarily within mitochondrial membranes, determined by western blot in vivo and in vitro. Significant increases in the rates of hepatocyte apoptosis, particularly early apoptosis, were observed in the OJ groups. However, there was a reverse in the rates of hepatocyte apoptosis after knockdown regulation of VDAC1 only within the cells of the OJ group. Conclusion: The up-regulation of VDAC in liver injury caused by obstructive jaundice may lead to increased early apoptosis of hepatocytes. | ||
| کلیدواژهها | ||
| Acute liver injury؛ Apoptosis؛ Mitochondria؛ Obstructive jaundice؛ VDAC1 | ||
| مراجع | ||
|
1. Bolduan F, Geisel D, Pahl S, Wree A, Tacke F. Painless jaundice with segmental obstructive cholestasis. J Hepatol 2023;79:e16-e18. 2. Lebedev SS, Tavobilov MM, Karpov AA, Abramov KA, Bochkov PO, Shevchenko RV, et al. Cytochrome P450 3A4 activity and genetic variants as predictors of liver failure in patients with obstructive jaundice. Free Radic Biol Med 2023;208:229-235. 3. Iacono C, Ruzzenente A, Campagnaro T, Bortolasi L, Valdegamberi A, Guglielmi A. Role of preoperative biliary drainage in jaundiced patients who are candidates for pancreatoduodenectomy or hepatic resection: Highlights and drawbacks. Ann Surg 2013;257:191-204. 4. Kosar NM, Tosun M, Polat C, Kahraman A, Arikan Y. Hepatocyte apoptotic index and p53 expression in obstructive jaundice rats. Bratisl Lek Listy 2014;115:352-356. 5. Zheng D, Liu J, Piao H, Zhu Z, Wei R, Liu K. ROS-triggered endothelial cell death mechanisms: Focus on pyroptosis, parthanatos, and ferroptosis. front Immunol 2022;13:1039241. 6. Sharma R, Anker SD. Cytokines, apoptosis and cachexia: The potential for TNF antagonism. Int J Cardiol 2002;85:161-171. 7. Rani R, Sharma A, Wang J, Kumar S, Polaki US, Gandhi CR. Endotoxin-stimulated hepatic stellate cells augment acetaminophen-induced hepatocyte injury. Am J Pathol 2022;192:518-535. 8. Kim DS, Song L, Wang J, Wu H, Gou W, Cui W, et al. Carbon monoxide inhibits islet apoptosis via induction of autophagy. Antioxid Redox Signal 2018;28:1309-1322. 9. Jeong SY, Seol DW. The role of mitochondria in apoptosis. BMB Rep 2008;41:11-22. 10. Zhong G, Wan F, Wu S, Jiang X, Tang Z, Zhang X, et al. Arsenic or/and antimony induced mitophagy and apoptosis associated with metabolic abnormalities and oxidative stress in the liver of mice. Sci Total Environ 2021;777:146082. 11. Deng X, Deng T, Ni Y, Zhan Y, Huang W, Liu J, et al. Cytochrome c modulates the mitochondrial signaling pathway and polymorphonuclear neutrophil apoptosis in bile duct-ligated rats. Exp Ther Med 2016;12:333-342. 12. Shoshan-Barmatz V, Shteinfer-Kuzmine A, Verma A. VDAC1 at the intersection of cell metabolism, apoptosis, and diseases. Biomolecules 2020;10: 1485-1524 13. Liu Y, Zhang H, Liu Y, Zhang S, Su P, Wang L, et al. Hypoxia-induced GPCPD1 depalmitoylation triggers mitophagy via regulating PRKN-mediated ubiquitination of VDAC1. Autophagy 2023;19:2443-2463. 14. Giorgio V, Guo L, Bassot C, Petronilli V, Bernardi P. Calcium and regulation of the mitochondrial permeability transition. Cell Calcium 2018;70:56-63 . 15. Karch J, Kwong JQ, Burr AR, Sargent MA, Elrod JW, Peixoto PM, et al. Bax and Bak function as the outer membrane component of the mitochondrial permeability pore in regulating necrotic cell. Elife 2013;2:e00772. 16. Scorrano L, Oakes SA, Opferman JT, Cheng EH, Sorcinelli MD, Pozzan T, et al. BAX and BAK regulation of endoplasmic reticulum Ca2+: A control point for apoptosis. Science 2003;300: 135-139. 17. Wu YL, Li ZL, Zhang XB, Liu H. Yinchenhao decoction attenuates obstructive jaundice-induced liver injury and hepatocyte apoptosis by suppressing protein kinase RNA-like endoplasmic reticulum kinase-induced pathway. World J Gastroenterol 2019;25:6205-6221. 18. Pan PH, Wang YY, Lin SY, Liao SL, Chen YF, Huang WC, et al. Plumbagin ameliorates bile duct ligation-induced cholestatic liver injury in rats. Biomed Pharmacother 2022;151:113133. 19. Liu XL, Li LJ, Chen Z. Isolation and primary culture of rat hepatocytes. Hepatobiliary Pancreat Dis Int 2002;1:77-79. 20. Rajathi S, Ramesh G, Kannan TA, Dharani P, Gnanadevi R. Liver in guinea pig: Scanning and transmission electron microscopic studies. Microsc Res Tech 2022;85:3391-3396. 21. Nicklas WJ, Youngster SK, Kindt MV, Heikkila RE. MPTP, MPP+ and mitochondrial function. Life Sci 1987;40:721-729. 22. Terada T, Nakanuma Y. Innervation of intrahepatic bile ducts and peribiliary glands in normal human livers, extrahepatic biliary obstruction and hepatolithiasis. An immunohistochemical study. J Hepatol 1989;9:141-148. 23. Chen HL, Wu SH, Hsu SH, Liou BY, Chen HL, Chang MH. Jaundice revisited: Recent advances in the diagnosis and treatment of inherited cholestatic liver diseases. J Biomed Sci 2018;25:75-87. 24. Iida A, Yoshidome H, Shida T, Kimura F, Shimizu H, Ohtsuka M, et al. Does prolonged biliary obstructive jaundice sensitize the liver to endotoxemia? Shock 2009;31:397-403. 25. Silina EV, Stupin VA, Abramov IS, Bolevich SB, Deshpande G, Achar RR, et al. Oxidative stress and free radical processes in tumor and non-tumor obstructive jaundice: Influence of disease duration, severity and surgical treatment on outcomes. Pathophysiology 2022;29:32-51. 26. Seo E, Kang H, Choi H, Choi W, Jun HS. Reactive oxygen species-induced changes in glucose and lipid metabolism contribute to the accumulation of cholesterol in the liver during aging. Aging Cell 2019;18:e12895. 27. Valdés S, Paredes SD, García Carreras C, Zuluaga P, Rancan L, Linillos-Pradillo B, et al. S-adenosylmethionine decreases bacterial translocation, proinflammatory cytokines, oxidative stress and apoptosis markers in hepatic ischemia-reperfusion injury in Wistar rats. Antioxidants (Basel) 2023;12:1539-1553. 28. Zhuang Y, Ortega-Ribera M, Thevkar Nagesh P, Joshi R, Huang H, Wang Y, et al. Bile acid-induced IRF3 phosphorylation mediates cell death, inflammatory responses, and fibrosis in cholestasis-induced liver and kidney injury via regulation of ZBP1. Hepatology. 2024 Apr 1;79:752-767. 29. Gramignoli R, Ranade AR, Venkataramanan R, Strom SC. Effects of pro-inflammatory cytokines on hepatic metabolism in primary human hepatocytes. Int J Mol Sci. 2022;23:14880. 30. Mansouri A, Gattolliat CH, Asselah T. Mitochondrial dysfunction and signaling in chronic liver diseases. Gastroenterology 2018;155:629-647. 31. Elrashidy RA, Zakaria EM, Hasan RA, Elmaghraby AM, Hassan DA, Abdelgalil RM, et al. Implication of endoplasmic reticulum stress and mitochondrial perturbations in remote liver injury after renal ischemia/reperfusion in rats: Potential protective role of azilsartan. Redox Rep 2024;29:2319963. 32. Schwabe RF, Luedde T. Apoptosis and necroptosis in the liver: A matter of life and death. Nat Rev Gastroenterol Hepatol 2018;15:738-752. 33. Geske FJ, Lieberman R, Strange R, Gerschenson LE. Early stages of p53-induced apoptosis are reversible. Cell Death Differ 2001;8:182-191. 34. Wang J, Xie L, Shi Y, Ao L, Cai F, Yan F. Early Detection and Reversal of Cell Apoptosis Induced by Focused Ultrasound-Mediated Blood-Brain Barrier Opening. ACS Nano 2021;15:14509-14521. 35. Ren F, Narita R, Rashidi AS, Fruhwürth S, Gao Z, Bak RO, et al. ER stress induces caspase-2-tBID-GSDME-dependent cell death in neurons lytically infected with herpes simplex virus type 2. EMBO J 2023;42:e113118. 36. Motoyama S, Kitamura M, Saito S, Minamiya Y, Suzuki H, Saito R, et al. Bcl-2 is located predominantly in the inner membrane and crista of mitochondria in rat liver. Biochem Biophys Res Commun 1998;249:628-636. 37. Pedrini S, Sau D, Guareschi S, Bogush M, Brown RH Jr, Naniche N, et al. ALS-linked mutant SOD1 damages mitochondria by promoting conformational changes in Bcl-2. Hum Mol Genet 2010;19:2974-2986. 38. Lambrecht R, Rudolf F, Ückert AK, Sladky VC, Phan TS, Jansen J, et al. Non-canonical BIM-regulated energy metabolism determines drug-induced liver necrosis. Cell Death Differ 2024;31:119-131. 39. Ott M, Norberg E, Zhivotovsky B, Orrenius S. Mitochondrial targeting of tBid/Bax: a role for the TOM complex?. Cell Death Differ. 2009;16:1075-1082. 40. Monaco G, Decrock E, Arbel N, van Vliet AR, La Rovere RM, De Smedt H, et al. The BH4 domain of anti-apoptotic Bcl-XL, but not that of the related Bcl-2, limits the voltage-dependent anion channel 1 (VDAC1)-mediated transfer of pro-apoptotic Ca2+ signals to mitochondria. J Biol Chem 2015;290:9150-9161. 41. Green DR. The Mitochondrial Pathway of Apoptosis Part II: The BCL-2 Protein Family. Cold Spring Harb Perspect Biol 2022;14:a041046. 42. Victorelli S, Salmonowicz H, Chapman J, Martini H, Vizioli MG, Riley JS, et al. Apoptotic stress causes mtDNA release during senescence and drives the SASP [published correction appears in Nature. 2024;625:E15. 43. Bauer TM, Murphy E. Role of mitochondrial calcium and the permeability transition pore in regulating cell death. Circ Res 2020;126:280-293. 44. Bonora M, Giorgi C, Pinton P. Molecular mechanisms and consequences of mitochondrial permeability transition. Nat Rev Mol Cell Biol 2022;23:266-285. 45. Yuan S, Fu Y, Wang X, Shi H, Huang Y, Song X, et al. Voltage-dependent anion channel 1 is involved in endostatin-induced endothelial cell apoptosis. FASEB J 2008;22:2809-2820. 46. Ivanova H, Vervliet T, Monaco G, Terry LE, Rosa N, Baker MR, et al. Bcl-2-protein family as modulators of IP3 receptors and other organellar Ca2+ channels. Cold Spring Harb Perspect Biol 2020;12:a035089. 47. Xian H, Liou YC. Loss of MIEF1/MiD51 confers susceptibility to BAX-mediated cell death and PINK1-PRKN-dependent mitophagy. Autophagy 2019;15:2107-2125. 48. Andrews TS, Nakib D, Perciani CT, Ma XZ, Liu L, Winter E, et al. Single-cell, single-nucleus, and spatial transcriptomics characterization of the immunological landscape in the healthy and PSC human liver. J Hepatol 2024;80:730-743. 49. Abe T, Nariyasu T, Nagai T, Hamamoto M, Hanzawa M, Hiroshima Y, et al. Obstructive jaundice with a biliary clot post-endoscopic sphincterotomy treated with clipping and endoscopic biliary stenting. Endoscopy 2021;53:E297-E300. 50. Fang Y, Gurusamy KS, Wang Q, Davidson BR, Lin H, Xie X, et al. Meta-analysis of randomized clinical trials on safety and efficacy of biliary drainage before surgery for obstructive jaundice. Br J Surg 2013;100:1589-1596. 51. Chen B, Trudeau MT, Maggino L, Ecker BL, Keele LJ, DeMatteo RP, et al. Defining the Safety profile for performing pancreatoduodenectomy in the setting of hyperbilirubinemia. Ann Surg Oncol 2020;27:1595-1605. | ||
|
آمار تعداد مشاهده مقاله: 485 تعداد دریافت فایل اصل مقاله: 368 |
||