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Abstract #54710 Published in IGR 15-3

RNAi screening identifies GSK3β as a regulator of DRP1 and the neuroprotection of lithium chloride against elevated pressure involved in downregulation of DRP1

Wu JH; Zhang SH; Gao FJ; Lei Y; Chen XY; Gao F; Zhang SJ; Sun XH
Neuroscience Letters 2013; 554: 99-104


Elevated intraocular pressure (IOP) is considered as the major risk factor for the loss of retinal ganglion cells (RGCs) and their axons in glaucoma. Emerging evidence suggests elevated IOP can induce Drp1 upregulation and mitochondrial fission, which is involved in cell death. However, the underlying mechanism for these effects remains unknown. The present study used RNAi screening to investigate the effects of 24 kinases associated with mitochondrial activities on DRP1 expression under hydrostatic pressure. We identified, for the first time, that glycogen synthase kinase 3 beta (GSK3β) knockdown suppressed the upregulation of DRP1 induced by elevated pressure. Use of the pharmacological inhibitor of GSK3β inhibitor, lithium chloride (LiCl), confirmed this result. Furthermore, we demonstrated that one of the mechanisms of lithium chloride neuroprotection might be via inhibition of mitochondrial fission through downregulation of Drp1.

Eye & ENT Hospital, Fudan University, 200032, China; Shanghai Key Laboratory of Visual Impairment and Restoration, 200032, China.

Full article

Classification:

3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
11.8 Neuroprotection (Part of: 11 Medical treatment)



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