title: Poly(ADP-ribose) polymerase mediates both cell death and ATP decreases in SIRT2 inhibitor AGK2-treated microglial BV2 cells.
abstract: Sirtuin 2 (SIRT2), a sirtuin family protein, is a tubulin deacetylase. Recent studies have indicated that SIRT2 plays a key role in programmed necrosis, and the SIRT2 inhibitor AGK2 can decrease the cell death both in a cellular model of Parkinson's disease and in an animal model of myocardial ischemia-reperfusion. However, there has been little information regarding the role of SIRT2 in microglial survival and functions, which play critical roles in multiple neurological disorders. Our current study found that AGK2 at 10 μM - a widely used AGK2 concentration - can induce both late-stage apoptosis and necrosis, as well as a decrease in the intracellular ATP levels of microglial BV2 cells. Our study also showed that both the AGK2-induced cell death and the AGK2-induced ATP decline are mediated by poly(ADP-ribose) polymerase (PARP) activation. Collectively, our study has provided the first evidence suggesting a significant role of SIRT2 in the basal survival of microglia, as well as a mechanism accounting for the effects of SIRT2 on intracellular ATP levels.
authors.affiliation: School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, PR China.
authors.forename: Yexin
authors.initials: Y
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Nie
authors.forename: Danhong
authors.initials: D
authors.lastname: Wu
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Xunbin
authors.initials: X
authors.lastname: Wei
authors.forename: Weihai
authors.initials: W
authors.lastname: Ying
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D005663:Furans / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011804:Quinolines / Q000494:pharmacology*; D056565:Sirtuin 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: C521855:AGK2 compound; D005663:Furans; D011804:Quinolines; D011064:Poly Adenosine Diphosphate Ribose; D000255:Adenosine Triphosphate; C474199:SIRT2 protein, human; D056565:Sirtuin 2