title: The anti-necrosis role of hypoxic preconditioning after acute anoxia is mediated by aldose reductase and sorbitol pathway in PC12 cells.
abstract: It has been demonstrated that hypoxic preconditioning (HP) enhances the survival ability of the organism against the subsequent acute anoxia (AA). However, it is not yet clear whether necrosis induced by AA can be prevented by HP, and what are the underlying mechanisms. In this study, we examined the effect of HP (10% O(2), 48 h) on necrosis induced by AA (0% O(2), 24 h) in PC12 cells. We found that HP delayed the regulatory volume decrease and reduced cell swelling after 24 h of exposure to AA. Since aldose reductase (AR) is involved in cell volume regulation, we detected AR mRNA expression with reverse transcription-polymerase chain reaction (RT-PCR) techniques. The AR mRNA level was dramatically elevated by HP. Furthermore, an HP-induced decrease in cell injury was reversed by berberine chloride (BB), the inhibitor of AR. In addition, sorbitol synthesized from glucose catalyzed by AR is directly related to cell volume regulation. Subsequently, we tested sorbitol content in the cytoplasm. HP clearly elevated sorbitol content, while BB inhibited the elevation induced by HP. Further study showed that a strong inhibitor of sorbitol permease, quinidine, completely reversed the protection induced by HP after AA. These data provide evidence that HP prevents necrosis induced by AA and is mediated by AR and sorbitol pathway.
authors.affiliation: Department of Brain Protection and Plasticity, Institute of Basic Medical Sciences, Taiping Rd 27, Beijing, 100850, People's Republic of China.
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Wu
authors.forename: Zi-Min
authors.initials: ZM
authors.lastname: Ma
authors.forename: Xue-Lai
authors.initials: XL
authors.lastname: Fan
authors.forename: Tong
authors.initials: T
authors.lastname: Zhao
authors.forename: Zhao-Hui
authors.initials: ZH
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Xiong
authors.forename: Kuan
authors.initials: K
authors.lastname: Zhang
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Zhu
authors.forename: Ming
authors.initials: M
authors.lastname: Fan
mesh_terms: D000449:Aldehyde Reductase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001599:Berberine / Q000494:pharmacology; D015687:Cell Hypoxia; D009336:Necrosis / Q000378:metabolism; D016716:PC12 Cells; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013012:Sorbitol / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D001599:Berberine; D013012:Sorbitol; D000449:Aldehyde Reductase