RGD Reference Report - Protein kinase C-delta mediates neuronal apoptosis in the retinas of diabetic rats via the Akt signaling pathway. - Rat Genome Database

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

Authors: Kim, YH  Kim, YS  Park, CH  Chung, IY  Yoo, JM  Kim, JG  Lee, BJ  Kang, SS  Cho, GJ  Choi, WS 
Citation: Kim YH, etal., Diabetes. 2008 Aug;57(8):2181-90. Epub 2008 Apr 28.
RGD ID: 4108490
Pubmed: PMID:18443201   (View Abstract at PubMed)
PMCID: PMC2494683   (View Article at PubMed Central)
DOI: DOI:10.2337/db07-1431   (Journal Full-text)

OBJECTIVE: Protein kinase C (PKC)-delta, an upstream regulator of the Akt survival pathway, contributes to cellular dysfunction in the pathogenesis of diabetes. Herein, we examined the role of PKC-delta 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-delta affects Akt signaling and cell death in OLETF rat retinas, we examined 1) PKC-delta 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-delta inhibitor, or small interfering RNAs (siRNAs) for PKC-delta and HSP90. RESULTS: In OLETF retinas from 35-week-old rats, ganglion cell death, PKC-delta 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-delta 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-delta activation contributes to neuro-retinal apoptosis in diabetic rats by inhibiting Akt-mediated signaling pathways.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
type 2 diabetes mellitus  ISOPik3r1 (Rattus norvegicus)4108490; 4108490protein:increased phosphorylation:retina (rat)RGD 
type 2 diabetes mellitus  IEP 4108490protein:increased phosphorylation:retina (rat)RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of neuron apoptotic process  IMP 4108490ganglion cellsRGD 
positive regulation of protein binding  IMP 4108490Akt1-Hsp90RGD 
positive regulation of protein serine/threonine kinase activity  IMP 4108490Akt1RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hsp90ab1  (heat shock protein 90 alpha family class B member 1)
Pik3r1  (phosphoinositide-3-kinase regulatory subunit 1)

Genes (Mus musculus)
Pik3r1  (phosphoinositide-3-kinase regulatory subunit 1)

Genes (Homo sapiens)
PIK3R1  (phosphoinositide-3-kinase regulatory subunit 1)


Additional Information