HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Kim, Y.-H. Articles by Choi, W.-S. PubMed PubMed Citation Articles by Kim, Y.-H. Articles by Choi, W.-S. Social Bookmarking                What's this?

Protein kinase C mediates neuronal apoptosis in the retinas of diabetic rats via the Akt signaling pathway

¹Department of Anatomy and Neurobiology and
²Ophthalmology, School of Medicine, Institute of Health Science, Gyeongsang National University, Jinju, Gyeongnam 660-751
³Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan, 680-749, S. Korea

Objective: Protein kinase C (PKC) , an upstream regulator of the Akt survival pathway, contributes to cellular dysfunction in the pathogenesis of diabetes. Herein we examined the role of PKC in neuronal apoptosis through Akt in the retinas of diabetic rats.

Research Design and Methods: We used retinas from 24- and 35-week-old male Otsuka Long-Evans Tokushima fatty (OLETF) diabetic and Long-Evans Tokushima Otsuka (LETO) non-diabetic rats. To assess whether PKC affects Akt signaling and cell death in OLETF rat retinas, we examined i) PKC activity and apoptosis, ii) protein levels of phosphatidylinositol 3-kinase (PI3K) p85, heat shock protein 90 (HSP90), and protein phosphatase 2A (PP2A), iii) Akt phosphorylation, and iv) Akt binding to HSP90 or PP2A in LETO and OLETF retinas in the presence or absence of rottlerin, a highly specific PKC inhibitor, or small interfering RNAs (siRNAs) for PKC and HSP90.

Results: In 35-week OLETF retinas, ganglion cell death, PKC and PP2A activity, and Akt-PP2A binding were significantly increased, and Akt phosphorylation and Akt-HSP90 binding were decreased as compared with 24-week OLETF and LETO rats. Rottlerin and PKC siRNA abrogated these effects in 35-week OLETF retinas. HSP90 siRNA significantly increased ganglion cell death and Akt-PP2A complexes and markedly decreased HSP90-Akt binding and Akt phosphorylation in 35-week LETO retinas as compared to non-treated LETO rats.

Conclusions: PKC activation contributes to neuro-retinal apoptosis in diabetic rats by inhibiting Akt-mediated signaling pathways.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?