title: Propofol Protects Against H2O2-Induced Oxidative Injury in Differentiated PC12 Cells via Inhibition of Ca(2+)-Dependent NADPH Oxidase.
abstract: Propofol (2,6-diisopropylphenol) is a widely used general anesthetic with anti-oxidant activities. This study aims to investigate protective capacity of propofol against hydrogen peroxide (H2O2)-induced oxidative injury in neural cells and whether the anti-oxidative effects of propofol occur through a mechanism involving the modulation of NADPH oxidase (NOX) in a manner of calcium-dependent. The rat differentiated PC12 cell was subjected to H2O2 exposure for 24 h to mimic a neuronal in vitro model of oxidative injury. Our data demonstrated that pretreatment of PC12 cells with propofol significantly reversed the H2O2-induced decrease in cell viability, prevented H2O2-induced morphological changes, and reduced the ratio of apoptotic cells. We further found that propofol attenuated the accumulation of malondialdehyde (biomarker of oxidative stress), counteracted the overexpression of NOX core subunit gp91(phox) (NOX2) as well as the NOX activity following H2O2 exposure in PC12 cells. In addition, blocking of L-type Ca(2+) channels with nimodipine reduced H2O2-induced overexpression of NOX2 and caspase-3 activation in PC12 cells. Moreover, NOX inhibitor apocynin alone or plus propofol neither induces a significant downregulation of NOX activity nor increases cell viability compared with propofol alone in the PC12 cells exposed to H2O2. These results demonstrate that the protective effects of propofol against oxidative injury in PC12 cells are mediated, at least in part, through inhibition of Ca(2+)-dependent NADPH oxidase.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, People's Republic of China.|Department of Anesthesiology, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College, Fujian Medical University, Fuzhou, 350001, People's Republic of China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, People's Republic of China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, People's Republic of China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, People's Republic of China.
authors.forename: Zhi-Bin
authors.initials: ZB
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, People's Republic of China.
authors.forename: Di-Han
authors.initials: DH
authors.lastname: Lu
authors.affiliation: Department of Anatomy, Zhongshan School of Medicine, Sun Yat-Sen University, No. 74 Zhongshan Road 2, Guangzhou, 510080, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Anatomy, Zhongshan School of Medicine, Sun Yat-Sen University, No. 74 Zhongshan Road 2, Guangzhou, 510080, People's Republic of China.
authors.forename: Ze-Min
authors.initials: ZM
authors.lastname: Ling
authors.affiliation: Department of Anatomy, Zhongshan School of Medicine, Sun Yat-Sen University, No. 74 Zhongshan Road 2, Guangzhou, 510080, People's Republic of China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, People's Republic of China. fengxiar1968@163.com.
authors.forename: Xia
authors.initials: X
authors.lastname: Feng
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000633:toxicity*; D042541:Intracellular Space / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism*; D000066829:Neuroprotection / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D015742:Propofol / Q000494:pharmacology*; D051381:Rats
chemical_list: D000098:Acetophenones; D018696:Neuroprotective Agents; D008315:Malondialdehyde; C056165:acetovanillone; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases; D053148:Caspase 3; D002118:Calcium; D015742:Propofol
keywords: Hydrogen peroxide; NADPH oxidase; Oxidative injury; PC12 cells; Propofol