title: Astaxanthin protects against MPP(+)-induced oxidative stress in PC12 cells via the HO-1/NOX2 axis.
abstract: BACKGROUND
  Although the etiology of PD remains unclear, increasing evidence has shown that oxidative stress plays an important role in its pathogenesis and that of other neurodegenerative disorders. NOX2, a cytochrome subunit of NOX, transports electrons across the plasma membrane to generate ROS, leading to physiological and pathological processes. Heme oxygenase-1 (HO-1) can be rapidly induced by oxidative stress and other noxious stimuli in the brain or other tissues. Astaxanthin (ATX), a carotenoid with antioxidant properties, is 100-1000 times more effective than vitamin E. The present study investigated the neuroprotective effects of ATX on MPP(+)-induced oxidative stress in PC12 cells.
  
  
  RESULTS
  MPP(+) significantly decreased MTT levels in a concentration-dependent manner. Hemin, SnPPIX and ATX didn't exhibit any cytotoxic effects on PC12 cells. Pretreatment with ATX (5, 10, 20 μM), caused intracellular ROS production in the MPP(+) group to decrease by 13.06%, 22.13%, and 27.86%, respectively. MPP(+) increased NOX2, NRF2 and HO-1 protein expression compared with control (p < 0.05). Co-treatment with hemin or ATX suppressed NOX2 expression (p < 0.01), and greatly increased NRF2 and HO-1 expression (p < 0.01). MPP(+) treatment up-regulated both NOX2 (p < 0.01) and HO-1 (p < 0.01) mRNA levels. Co-treatment with hemin or ATX significantly increased HO-1 mRNA levels (p < 0.01), and decreased NOX2 mRNA levels (p < 0.01). MPP(+) increased NOX2 and HO-1 expression with considerable fluorescence extending out from the perinuclear region toward the periphery; this was attenuated by DPI. Co-treatment with hemin or ATX significantly up-regulated HO-1 expression and decreased NOX2 expression with considerable fluorescence intensity (stronger than the control and MPP(+) groups).
  
  
  CONCLUSIONS
  ATX suppresses MPP(+)-induced oxidative stress in PC12 cells via the HO-1/NOX2 axis. ATX should be strongly considered as a potential neuroprotectant and adjuvant therapy for patients with Parkinson's disease.
authors.affiliation: Department of Neurology, Fujian Institute of Geriatrics, The Affiliated Union Hospital of Fujian Medical University, 29 Xinquan Road, Fuzhou, Fujian 350001, China. unionqyye@163.com
authors.forename: Qinyong
authors.initials: Q
authors.lastname: Ye
authors.forename: Bixia
authors.initials: B
authors.lastname: Huang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.forename: Yuangui
authors.initials: Y
authors.lastname: Zhu
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Chen
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000037:antagonists & inhibitors*; D000975:Antioxidants / Q000494:pharmacology*; D002395:Catecholamines / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006427:Hemin / Q000494:pharmacology; D048288:Imidazolines / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000096:biosynthesis*; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D017382:Reactive Oxygen Species / Q000378:metabolism; D024341:Xanthophylls / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D002395:Catecholamines; D018491:Dopamine Agonists; D048288:Imidazolines; D008562:Membrane Glycoproteins; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495637:Nfe2l2 protein, rat; D017382:Reactive Oxygen Species; D024341:Xanthophylls; D006427:Hemin; C005948:astaxanthine; C011775:(3,4-dihydroxyphenylamino)-2-imidazoline; D051547:Heme Oxygenase-1; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D015655:1-Methyl-4-phenylpyridinium