advertisement
Abstract #24573 Published in IGR 11-4
Pilocarpine Protects Cobalt Chloride-induced Apoptosis of RGC-5 Cells: Involvement of Muscarinic Receptors and HIF-1(alpha) Pathway
Zhu X; Zhou W; Cui Y; Zhu L; Li J; Feng X; Shao B; Qi H; Zheng J; Wang HCellular and molecular neurobiology 2009; 1-9
The retina is the most metabolically active tissue in the human body and hypoxia-induced retinal ganglion cell (RGC) death has been implicated in glaucomatous optic neuropathy. The aim of this study is to determine whether muscarinic receptor agonist pilocarpine, a classic antiglaucoma drug, possesses neuroprotection against cobalt chloride (CoCl(2))-mimetic hypoxia-induced apoptosis of rat retinal ganglion cells (RGC-5 cells) and its underlying mechanisms. Cell viability was determined by Cell Counting Kit-8 assay and apoptosis was examined by annexin V and mitochondrial membrane potential (MMP) assays. Expressions of hypoxia-induced factor-1(alpha) (HIF-1(alpha)), p53, and BNIP3 were investigated by quantitative real-time PCR and western blot analysis. After treatment of 200 (mu)M CoCl(2) for 24 h, RGC-5 cells showed a marked decrease of cell viability by approximately 30%, increased apoptosis rate and obvious decline in MMP, which could largely be reversed by the pretreatment of 1 (mu)M pilocarpine mainly via the activation of muscarinic receptors. Meanwhile, pretreatment of 1 (mu)M pilocarpine could significantly prevent CoCl(2)-induced HIF-1(alpha) translocation from cytoplasm to nucleus and down-regulate the expression of HIF-1(alpha), p53, and BNIP3. These studies demonstrated that pilocarpine had effective protection against hypoxia-induced apoptosis in RGCs via muscarinic receptors and HIF-1(alpha) pathway. The findings suggest that HIF-1(alpha) pathway as a "master switch" may be used as a therapeutic target in the cholinergic treatment of glaucoma.
H. Chen. Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China. hongzhuan_chen@hotmail.com
Classification:
11.2 Cholinergic drugs (Part of: 11 Medical treatment)
3.6 Cellular biology (Part of: 3 Laboratory methods)
11.8 Neuroprotection (Part of: 11 Medical treatment)
