Resveratrol Ameliorates Microcystin-LR-Induced Testis Germ Cell Apoptosis in Rats Via SIRT1 Signaling Pathway Activation

Overview

Journal Toxins (Basel)

Publisher MDPI

Specialty Toxicology

Date 2018 Jun 13

PMID 29890735

Citations 9

Authors

Haohao Liu

Shenshen Zhang

Chuanrui Liu

Jinxia Wu

Yueqin Wang

Le Yuan

Xingde Du

Rui Wang

Phelisters Wegesa Marwa

Donggang Zhuang

Xuemin Cheng

Huizhen Zhang

Affiliations

Soon will be listed here.

Abstract

Microcystin-leucine arginine (MC-LR), a cyclic heptapeptide produced by cyanobacteria, is a strong reproductive toxin. Studies performed in rat Sertoli cells and Chinese hamster ovary cells have demonstrated typical apoptosis after MC-LR exposure. However, little is known on how to protect against the reproductive toxicity induced by MC-LR. The present study aimed to explore the possible molecular mechanism underlying the anti-apoptosis and protective effects of resveratrol (RES) on the co-culture of Sertoli⁻germ cells and rat testes. The results demonstrated that MC-LR treatment inhibited the proliferation of Sertoli⁻germ cells and induced apoptosis. Furthermore, sirtuin 1 (SIRT1) and Bcl-2 were inhibited, while p53 and Ku70 acetylation, Bax expression, and cleaved caspase-3 were upregulated by MC-LR. However, RES pretreatment ameliorated MC-LR-induced apoptosis and SIRT1 inhibition, and downregulated the MC-LR-induced increase in p53 and Ku70 acetylation, Bax expression, and caspase-3 activation. In addition, RES reversed the MC-LR-mediated reduction in Ku70 binding to Bax. The present study indicated that the administration of RES could ameliorate MC-LR-induced Sertoli⁻germ cell apoptosis and protect against reproductive toxicity in rats by stimulating the SIRT1/p53 pathway, suppressing p53 and Ku70 acetylation and enhancing the binding of Ku70 to Bax.

Citing Articles

Protective Effects of Resveratrol Against Perfluorooctanoic Acid-Induced Testicular and Epididymal Toxicity in Adult Rats Exposed During Their Prepubertal Period.

Pavani R, Venkaiah K, Prakasam P, Dirisala V, Krishna P, Kishori B Toxics. 2025; 13(2).

PMID: 39997926 PMC: 11860439. DOI: 10.3390/toxics13020111.

Resveratrol: potential application in safeguarding testicular health.

Zhang X, Yi R, Liu Y, Ma J, Xu J, Tian Q EPMA J. 2024; 15(4):643-657.

PMID: 39635023 PMC: 11612077. DOI: 10.1007/s13167-024-00377-1.

Sirtuins in intervertebral disc degeneration: current understanding.

Shen J, Lan Y, Ji Z, Liu H Mol Med. 2024; 30(1):44.

PMID: 38553713 PMC: 10981339. DOI: 10.1186/s10020-024-00811-0.

Resveratrol Promotes Proliferation, Antioxidant Properties, and Progesterone Production in Yak () Granulosa Cells.

Jiang X, Ma Y, Gong S, Zi X, Zhang D Animals (Basel). 2024; 14(2).

PMID: 38254409 PMC: 10812796. DOI: 10.3390/ani14020240.

The Effects of Resveratrol, Gallic Acid, and Piperine on the Expression of miR-17, miR-92b, miR-181a, miR-222, BAX, BCL-2, MCL-1, WT1, c-Kit, and CEBPA in Human Acute Myeloid Leukemia Cells and Their Roles in Apoptosis.

Iravani Saadi M, Moayedi J, Hosseini F, Rostamipour H, Karimi Z, Rahimian Z Biochem Genet. 2023; 62(4):2958-2974.

PMID: 38062274 DOI: 10.1007/s10528-023-10582-8.

References

Li M, Li J, Gu Q, An J, Cao L, Yang H . EGCG induces lung cancer A549 cell apoptosis by regulating Ku70 acetylation. Oncol Rep. 2016; 35(4):2339-47. DOI: 10.3892/or.2016.4587. View

Sinha N, Adhikari N, Saxena D . Effect of endosulfan on the enzymes of polyol pathway in rat sertoli-germ cell coculture. Bull Environ Contam Toxicol. 2001; 67(6):821-7. DOI: 10.1007/s001280196. View

Howitz K, Bitterman K, Cohen H, Lamming D, Lavu S, Wood J . Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003; 425(6954):191-6. DOI: 10.1038/nature01960. View

Zhang D, Xie P, Liu Y, Qiu T . Transfer, distribution and bioaccumulation of microcystins in the aquatic food web in Lake Taihu, China, with potential risks to human health. Sci Total Environ. 2009; 407(7):2191-9. DOI: 10.1016/j.scitotenv.2008.12.039. View

Qin W, Xu L, Zhang X, Wang Y, Meng X, Miao A . Endoplasmic reticulum stress in murine liver and kidney exposed to microcystin-LR. Toxicon. 2010; 56(8):1334-41. DOI: 10.1016/j.toxicon.2010.07.017. View

Ben Salem I, Boussabbeh M, Pires Da Silva J, Guilbert A, Bacha H, Abid-Essefi S . SIRT1 protects cardiac cells against apoptosis induced by zearalenone or its metabolites α- and β-zearalenol through an autophagy-dependent pathway. Toxicol Appl Pharmacol. 2016; 314:82-90. DOI: 10.1016/j.taap.2016.11.012. View

Codd G, Morrison L, Metcalf J . Cyanobacterial toxins: risk management for health protection. Toxicol Appl Pharmacol. 2005; 203(3):264-72. DOI: 10.1016/j.taap.2004.02.016. View

Park S, Ahmad F, Philp A, Baar K, Williams T, Luo H . Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell. 2012; 148(3):421-33. PMC: 3431801. DOI: 10.1016/j.cell.2012.01.017. View

Wu J, Shao S, Zhou F, Wen S, Chen F, Han X . Reproductive toxicity on female mice induced by microcystin-LR. Environ Toxicol Pharmacol. 2013; 37(1):1-6. DOI: 10.1016/j.etap.2013.10.012. View

10.

Wang X, Wu L, Zhao L, Sun L, Liu H, Liu G . SIRT1 activator ameliorates the renal tubular injury induced by hyperglycemia in vivo and in vitro via inhibiting apoptosis. Biomed Pharmacother. 2016; 83:41-50. DOI: 10.1016/j.biopha.2016.06.009. View

11.

Lieber M . The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem. 2010; 79:181-211. PMC: 3079308. DOI: 10.1146/annurev.biochem.052308.093131. View

12.

Yi J, Luo J . SIRT1 and p53, effect on cancer, senescence and beyond. Biochim Biophys Acta. 2010; 1804(8):1684-9. PMC: 2989880. DOI: 10.1016/j.bbapap.2010.05.002. View

13.

Luo J, Nikolaev A, Imai S, Chen D, Su F, SHILOH A . Negative control of p53 by Sir2alpha promotes cell survival under stress. Cell. 2001; 107(2):137-48. DOI: 10.1016/s0092-8674(01)00524-4. View

14.

Miyashita T, Krajewski S, Krajewska M, Wang H, Lin H, Liebermann D . Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene. 1994; 9(6):1799-805. View

15.

Jang J, Huh Y, Cho H, Lee B, Park J, Hwang D . SIRT1 Enhances the Survival of Human Embryonic Stem Cells by Promoting DNA Repair. Stem Cell Reports. 2017; 9(2):629-641. PMC: 5549766. DOI: 10.1016/j.stemcr.2017.06.001. View

16.

Zhou Y, Yuan J, Wu J, Han X . The toxic effects of microcystin-LR on rat spermatogonia in vitro. Toxicol Lett. 2012; 212(1):48-56. DOI: 10.1016/j.toxlet.2012.05.001. View

17.

Puddick J, Prinsep M, Wood S, Kaufononga S, Cary S, Hamilton D . High levels of structural diversity observed in microcystins from Microcystis CAWBG11 and characterization of six new microcystin congeners. Mar Drugs. 2014; 12(11):5372-95. PMC: 4245536. DOI: 10.3390/md12115372. View

18.

Chen C, Liu W, Wang L, Li J, Chen Y, Jin J . Pathological damage and immunomodulatory effects of zebrafish exposed to microcystin-LR. Toxicon. 2016; 118:13-20. DOI: 10.1016/j.toxicon.2016.04.030. View

19.

Zhang S, Liu C, Li Y, Imam M, Huang H, Liu H . Novel Role of ER Stress and Autophagy in Microcystin-LR Induced Apoptosis in Chinese Hamster Ovary Cells. Front Physiol. 2016; 7:527. PMC: 5099254. DOI: 10.3389/fphys.2016.00527. View

20.

Anekonda T, Adamus G . Resveratrol prevents antibody-induced apoptotic death of retinal cells through upregulation of Sirt1 and Ku70. BMC Res Notes. 2008; 1:122. PMC: 2633309. DOI: 10.1186/1756-0500-1-122. View