Mechanisms of neuroprotection of silent information regulation 2 homolog 3 against hypoxic injury in hypoxic preconditioning
10.3760/cma.j.issn.1006-7876.2011.07.011
- VernacularTitle:沉默信息调节因子3参与缺氧预处理对神经元的保护作用
- Author:
Chaoying LI
;
Ling LI
;
Jia ZHAO
;
Huan WEI
;
Na LI
;
Ying WANG
;
Yuqian TAO
- Publication Type:Journal Article
- Keywords:
Anoxia;
Ischemic preconditioning;
Reactive oxygen species;
Sirtuin 3;
Transcription factors;
Heat-shock proteins;
Superoxide dismutase
- From:
Chinese Journal of Neurology
2011;44(7):482-486
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanisms underlying neuroprotection of silent information regulation 2 homolog 3 ( SIRT3 ) against hypoxia via preconditioning.Methods PG12 cells were randomly divided into control,hypoxic preconditioning ( Hyp),Hyp with oxygen-glucose deprivation (OGD) and OGD.MTT assay and DAPI staining were used to evaluate cellular viability.MitoSOX Red was used to measure the production of mitochondrial superoxide.The protein expression of SIRT3,PGC-1α and MnSOD were assessed by Western blot.Recombinant SIRT3 was also given to further investigate its roles in hypoxic preconditioning.Results The preconditioned PC12 cells had a higher survival rate.When expressed as a percentage of the control group,MTT values following 6 h OGD were around 51.0% in the OGD group but around 74.7% in the Hyp + OGD group ( F = 56,P < 0.01).Mitochondrial ROS after Hyp was less than the OGD group.Both Hyp + OGD and OGD increased the expression of SIRT3,PGC-1α and MnSOD proteins,and these increases were greater after Hyp + OGD.Similarly,the application of recombinant SIRT3 to OGD also further increased the expression of these proteins.Conclusions Hypoxic preconditioning can protect PC12 cells against hypoxic injury.One possible mechanism of hypoxic preconditioning is via SIRT3 to upregulate PGC-la and,in turn,MnSOD to reduce generation of ROS.