Phytohormone Abscisic Acid Protects Human Neuroblastoma SH-SY5Y Cells Against 6-Hydroxydopamine-Induced Neurotoxicity Through Its Antioxidant and Antiapoptotic Properties.

Abstract

Parkinson's disease (PD) is a destroying and prevalent neurodegenerative disease that is characterized by a progressive death of midbrain dopaminergic neurons. It is important to understand the possible neuroprotective effects of reagents that rescue the neurons from death and apoptosis. In this study, we investigated the effects of abscisic acid (ABA) on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in human dopaminergic neuroblastoma SH-SY5Y cell line as an in vitro model of PD. Cell damage was induced by 150 μM 6-OHDA and the cell viability was examined by 2-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2-tetrazolium bromide (MTT) assay. Reactive oxygen species (ROS) and mitochondrial membrane potential were assessed by fluorescence probe methods. Biochemical markers of apoptosis were also determined by immunoblotting. The data showed that 6-OHDA caused a significant loss of cell viability and mitochondrial membrane potential. In addition, intracellular ROS, cleaved caspase-3, Bax:Bcl-2 ratio, and cytochrome c release were significantly increased in 6-OHDA-incubated cells. ABA (100 μM) elicited a significant protective effect and reduced biochemical markers of cell damage and death. Blockage of peroxisome proliferator-activated receptor (PPAR)γ completely prevented the effect of ABA on 6-OHDA-induced cell toxicity. The results suggest that ABA has neuroprotective property against 6-OHDA-induced neurotoxicity, which is performed through PPARγ signaling. However, ABA antioxidant and antiapoptotic properties are involved, at least in part, in such protection.