Abstract
BackgroundAlthough 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.ResultsMPP+ 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).ConclusionsATX 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.
Highlights
The etiology of Parkinson’s disease (PD) remains unclear, increasing evidence has shown that oxidative stress plays an important role in its pathogenesis and that of other neurodegenerative disorders
Effects of MPP+, hemin, tin protoporphyrin IX dichloride (SnPPIX), Diphenyleneiodonium chloride (DPI) and ATX on cell viability To evaluate the viability of differentiated PC12 cells after exposure to oxidative injury, differentiated PC12 cells were treated with different concentrations of MPP+ (125–2000 μmoL/L) for 24 h
The results indicate that MPP+ treatment upregulated Nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), NRF2 and Heme oxygenase-1 (HO-1) expression at both the mRNA and protein levels
Summary
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. The present study investigated the neuroprotective effects of ATX on MPP+-induced oxidative stress in PC12 cells. Several mechanisms have been proposed to explain the pathogenesis of PD, including the production of reactive oxygen species (ROS), generated by dopamine dopamine uptake and eliciting dopaminergic neuronal loss. NOX2 is a cytochrome subunit of NOX that transports electrons across the plasma membrane to generate ROS and promotes physiological and pathological processes. Activation of phagocytic NOX2 has been studied mainly in microglia, where it plays a role in inflammation, but may contribute to neuronal death in pathological conditions [10]. Microglia-mediated NOX2 activation, caused by dopaminergic neuron injury, may play a role in the loss of dopaminergic neurons
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