We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Protein Kinase C-σ Mediates Neuronal Apoptosis in the Retinas of Diabetic Rats via the Akt Signaling Pathway.
- Authors
Young-Hee Kim; Yoon-Sook Kim; Chang-Hwan Park; In-Yong Chung; Ji-Myong Yoo; Jae-Geun Kim; Byung-Ju Lee; Sang-Soo Kang; Gyeong-Jae Cho; Wan-Sung Choi
- Abstract
OBJECTIVE--Protein kinase C (PKC)-δ, an upstream regulator of the Akt survival pathway, contributes to cellular dysfunction in the pathogenesis of diabetes. Herein, we examined the role of PKC-δ 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) nondiabetic rats. To assess whether PKC-δ affects Akt signaling and cell death in OLETF rat retinas, we examined 1) PKC-δ activity and apoptosis; 2) protein levels of phosphatidylinositol 3-kinase (PI 3-kinase) p85, heat shock protein 90 (HSP90), and protein phosphatase 2A (PP2A); 3) Akt phosphorylation; and 4) Akt binding to HSP90 or PP2A in LETO and OLETF retinas in the presence or absence of rottlerin, a highly specific PKC-δ inhibitor, or small interfering RNAs (siRNAs) for PKC-δ and HSP90. RESULTS--In OLETF retinas from 35-week-old rats, ganglion cell death, PKC-δ and PP2A activity, and Akt-PP2A binding were significantly increased and Akt phosphorylation and Akt-HSP90 binding were decreased compared with retinas from 24-week-old OLETF and LETO rats. Rottlerin and PKC-δ siRNA abrogated these effects in OLETF retinas from 35-week-old rats. HSP90 siRNA significantly increased ganglion cell death and Akt-PP2A complexes and markedly decreased HSP90-Akt binding and Akt phosphorylation in LETO retinas from 35-week-old rats compared with those from nontreated LETO rats. CONCLUSIONS--PKC-δ activation contributes to neuro-retinal apoptosis in diabetic rats by inhibiting Akt-mediated signaling pathways. Diabetes 57:2181-2190, 2008
- Subjects
PROTEIN kinase C; APOPTOSIS; RETINA; DIABETES; HEAT shock proteins; LABORATORY rats
- Publication
Diabetes, 2008, Vol 57, Issue 8, p2181
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db07-1431