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

BMC Neuroscience

Xiaochun Chen¹  Yuangui Zhu¹  Xiaodong Zhang¹  Bixia Huang¹  Qinyong Ye¹ 

[1] Department of Neurology, Fujian Institute of Geriatrics, The Affiliated Union Hospital of Fujian Medical University, 29 Xinquan Road, Fuzhou, Fujian, 350001, China

关键词: HO-1;    NOX2;    MPP⁺;    PC12 cells;    Astaxanthin;    Parkinson’s disease;   

Others  :  1140625
DOI  :  10.1186/1471-2202-13-156

 received in 2012-05-11, accepted in 2012-12-26,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 ye et al.; licensee BioMed Central Ltd.

【 图 表 】

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