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Pilocarpine Protects Cobalt Chloride-induced Apoptosis of RGC-5 Cells: Involvement of Muscarinic Receptors and HIF-1α Pathway.
- Source :
- Cellular & Molecular Neurobiology; Apr2010, Vol. 30 Issue 3, p427-435, 9p, 2 Color Photographs, 1 Chart, 5 Graphs
- Publication Year :
- 2010
-
Abstract
- 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<subscript>2</subscript>)-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-1α (HIF-1α), p53, and BNIP3 were investigated by quantitative real-time PCR and western blot analysis. After treatment of 200 μM CoCl<subscript>2</subscript> 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 μM pilocarpine mainly via the activation of muscarinic receptors. Meanwhile, pretreatment of 1 μM pilocarpine could significantly prevent CoCl<subscript>2</subscript>-induced HIF-1α translocation from cytoplasm to nucleus and down-regulate the expression of HIF-1α, p53, and BNIP3. These studies demonstrated that pilocarpine had effective protection against hypoxia-induced apoptosis in RGCs via muscarinic receptors and HIF-1α pathway. The findings suggest that HIF-1α pathway as a “master switch” may be used as a therapeutic target in the cholinergic treatment of glaucoma. [ABSTRACT FROM AUTHOR]
- Subjects :
- PILOCARPINE
APOPTOSIS
CELL death
MUSCARINIC receptors
RETINAL ganglion cells
Subjects
Details
- Language :
- English
- ISSN :
- 02724340
- Volume :
- 30
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Cellular & Molecular Neurobiology
- Publication Type :
- Academic Journal
- Accession number :
- 50130994
- Full Text :
- https://doi.org/10.1007/s10571-009-9467-2