Journal Article

Astaxanthin protects against MPP+-induced oxidative stress in PC12 cells via the HO-1/NOX2 axis

Huang, Bixia, Chen, Xiaochun, Zhang, Xiaodong, Ye, Qinyong, Zhu, Yuangui

2012

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: 1-Methyl-4-phenylpyridinium - antagonists & inhibitors / Algae / Animal Models / Antioxidants / Antioxidants - pharmacology / Apoptosis / Astaxanthin / Biomedical and Life Sciences / Biomedicine / Catecholamines - pharmacology / Cell culture / Cell Survival - drug effects / Cells / CYBB protein / Cytotoxicity / Development and progression / Dopamine / Dopamine Agonists - pharmacology / Drug Interactions / Electron transport / Enzymes / Fluorescence / Fluorides / Gene Expression Regulation - drug effects / Heme / Heme oxygenase (decyclizing) / Heme Oxygenase-1 - biosynthesis / Hemin / Hemin - pharmacology / HO-1 / Imidazolines - pharmacology / Membrane Glycoproteins - biosynthesis / Mitochondria / Movement disorders / MPP / mRNA / NADPH Oxidase 2 / NADPH Oxidases - biosynthesis / Nervous system diseases / Neurobiology / Neurobiology of disease / Neurodegenerative diseases / Neurons / Neuroprotection / Neuroprotective agents / Neuroprotective Agents - pharmacology / Neurosciences / NF-E2-Related Factor 2 - biosynthesis / NOX2 / Oxidative stress / Oxidative Stress - drug effects / Pain perception / Parkinson's disease / Pathogenesis / PC12 Cells / Pheochromocytoma cells / Physiological aspects / Proteins / Reactive Oxygen Species - metabolism / Research Article / RNA / Rodents / Sodium / Studies / Tin protoporphyrin / Vitamin E / Xanthophylls - pharmacology