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Resveratrol attenuates methylglyoxal-induced mitochondrial dysfunction and apoptosis by Sestrin2 induction.
Toxicol Appl Pharmacol. 2014 Oct 15; 280(2):314-22.TA

Abstract

Methylglyoxal is found in high levels in the blood and other tissues of diabetic patients and exerts deleterious effects on cells and tissues. Previously, we reported that resveratrol, a polyphenol in grapes, induced the expression of Sestrin2 (SESN2), a novel antioxidant protein, and inhibited hepatic lipogenesis. This study investigated whether resveratrol protects cells from the methylglyoxal-induced toxicity via SESN2 induction. Methylglyoxal significantly induced cell death in HepG2 cells. However, cells pretreated with resveratrol were rescued from methylglyoxal-induced apoptosis. Resveratrol attenuated glutathione (GSH) depletion and ROS production promoted by methylglyoxal. Moreover, mitochondrial damage was observed by methylglyoxal treatment, but resveratrol restored mitochondrial function, as evidenced by the observed lack of mitochondrial permeability transition and increased ADP/ATP ratio. Resveratrol treatment inhibited SESN2 depletion elicited by methylglyoxal. SESN2 overexpression repressed methylglyoxal-induced mitochondrial dysfunction and apoptosis. Likewise, rotenone-induced cytotoxicity was not observed in SESN2 overexpressed cells. Furthermore, siRNA knockdown of SESN2 reduced the ability of resveratrol to prevent methylglyoxal-induced mitochondrial permeability transition. In addition, when mice were exposed to methylglyoxal after infection of Ad-SESN2, the plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and GSH depletion by methylglyoxal in liver was reduced in Ad-SESN2 infected mice. Our results demonstrated that resveratrol is capable of protecting cells from methylglyoxal-induced mitochondrial dysfunction and oxidative stress via SESN2 induction.

Authors+Show Affiliations

College of Pharmacy, Chosun University, Gwangju 501-759, South Korea.College of Pharmacy, Chosun University, Gwangju 501-759, South Korea.College of Pharmacy, Chosun University, Gwangju 501-759, South Korea.College of Pharmacy, Chosun University, Gwangju 501-759, South Korea.College of Pharmacy, Chosun University, Gwangju 501-759, South Korea. Electronic address: smshin@chosun.ac.kr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25151220

Citation

Seo, Kyuhwa, et al. "Resveratrol Attenuates Methylglyoxal-induced Mitochondrial Dysfunction and Apoptosis By Sestrin2 Induction." Toxicology and Applied Pharmacology, vol. 280, no. 2, 2014, pp. 314-22.
Seo K, Seo S, Han JY, et al. Resveratrol attenuates methylglyoxal-induced mitochondrial dysfunction and apoptosis by Sestrin2 induction. Toxicol Appl Pharmacol. 2014;280(2):314-22.
Seo, K., Seo, S., Han, J. Y., Ki, S. H., & Shin, S. M. (2014). Resveratrol attenuates methylglyoxal-induced mitochondrial dysfunction and apoptosis by Sestrin2 induction. Toxicology and Applied Pharmacology, 280(2), 314-22. https://doi.org/10.1016/j.taap.2014.08.011
Seo K, et al. Resveratrol Attenuates Methylglyoxal-induced Mitochondrial Dysfunction and Apoptosis By Sestrin2 Induction. Toxicol Appl Pharmacol. 2014 Oct 15;280(2):314-22. PubMed PMID: 25151220.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Resveratrol attenuates methylglyoxal-induced mitochondrial dysfunction and apoptosis by Sestrin2 induction. AU - Seo,Kyuhwa, AU - Seo,Suho, AU - Han,Jae Yun, AU - Ki,Sung Hwan, AU - Shin,Sang Mi, Y1 - 2014/08/20/ PY - 2014/05/02/received PY - 2014/08/03/revised PY - 2014/08/13/accepted PY - 2014/8/25/entrez PY - 2014/8/26/pubmed PY - 2015/2/11/medline KW - Methylglyoxal KW - Mitochondrial dysfunction KW - Oxidative stress KW - Reactive oxygen species KW - Resveratrol KW - Sestrin2 SP - 314 EP - 22 JF - Toxicology and applied pharmacology JO - Toxicol. Appl. Pharmacol. VL - 280 IS - 2 N2 - Methylglyoxal is found in high levels in the blood and other tissues of diabetic patients and exerts deleterious effects on cells and tissues. Previously, we reported that resveratrol, a polyphenol in grapes, induced the expression of Sestrin2 (SESN2), a novel antioxidant protein, and inhibited hepatic lipogenesis. This study investigated whether resveratrol protects cells from the methylglyoxal-induced toxicity via SESN2 induction. Methylglyoxal significantly induced cell death in HepG2 cells. However, cells pretreated with resveratrol were rescued from methylglyoxal-induced apoptosis. Resveratrol attenuated glutathione (GSH) depletion and ROS production promoted by methylglyoxal. Moreover, mitochondrial damage was observed by methylglyoxal treatment, but resveratrol restored mitochondrial function, as evidenced by the observed lack of mitochondrial permeability transition and increased ADP/ATP ratio. Resveratrol treatment inhibited SESN2 depletion elicited by methylglyoxal. SESN2 overexpression repressed methylglyoxal-induced mitochondrial dysfunction and apoptosis. Likewise, rotenone-induced cytotoxicity was not observed in SESN2 overexpressed cells. Furthermore, siRNA knockdown of SESN2 reduced the ability of resveratrol to prevent methylglyoxal-induced mitochondrial permeability transition. In addition, when mice were exposed to methylglyoxal after infection of Ad-SESN2, the plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and GSH depletion by methylglyoxal in liver was reduced in Ad-SESN2 infected mice. Our results demonstrated that resveratrol is capable of protecting cells from methylglyoxal-induced mitochondrial dysfunction and oxidative stress via SESN2 induction. SN - 1096-0333 UR - https://www.unboundmedicine.com/medline/citation/25151220/Resveratrol_attenuates_methylglyoxal_induced_mitochondrial_dysfunction_and_apoptosis_by_Sestrin2_induction_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-008X(14)00303-2 DB - PRIME DP - Unbound Medicine ER -