RNAi screening identifies GSK3ß as a regulator of DRP1 and the neuroprotection of lithium chloride against elevated pressure involved in downregulation of DRP1.
Neurosci Lett
; 554: 99-104, 2013 Oct 25.
Article
in En
| MEDLINE
| ID: mdl-24025791
ABSTRACT
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 (GSK3ß) knockdown suppressed the upregulation of DRP1 induced by elevated pressure. Use of the pharmacological inhibitor of GSK3ß 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lithium Chloride
/
Neuroprotective Agents
/
Dynamins
/
Glycogen Synthase Kinase 3
/
RNA Interference
/
Retinal Pigment Epithelium
Type of study:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Screening_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Neurosci Lett
Year:
2013
Document type:
Article
Affiliation country:
China
Publication country:
IE
/
IRELAND
/
IRLANDA