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Protein Kinase C-δ Mediates Neuronal Apoptosis in the Retinas of Diabetic Rats via the Akt Signaling Pathway
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 ret...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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American Diabetes Association
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2494683/ https://www.ncbi.nlm.nih.gov/pubmed/18443201 http://dx.doi.org/10.2337/db07-1431 |
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author | Kim, Young-Hee Kim, Yoon-Sook Park, Chang-Hwan Chung, In-Yong Yoo, Ji-Myong Kim, Jae-Geun Lee, Byung-Ju Kang, Sang-Soo Cho, Gyeong-Jae Choi, Wan-Sung |
author_facet | Kim, Young-Hee Kim, Yoon-Sook Park, Chang-Hwan Chung, In-Yong Yoo, Ji-Myong Kim, Jae-Geun Lee, Byung-Ju Kang, Sang-Soo Cho, Gyeong-Jae Choi, Wan-Sung |
author_sort | Kim, Young-Hee |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2494683 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-24946832009-08-01 Protein Kinase C-δ Mediates Neuronal Apoptosis in the Retinas of Diabetic Rats via the Akt Signaling Pathway Kim, Young-Hee Kim, Yoon-Sook Park, Chang-Hwan Chung, In-Yong Yoo, Ji-Myong Kim, Jae-Geun Lee, Byung-Ju Kang, Sang-Soo Cho, Gyeong-Jae Choi, Wan-Sung Diabetes Complications 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. American Diabetes Association 2008-08 /pmc/articles/PMC2494683/ /pubmed/18443201 http://dx.doi.org/10.2337/db07-1431 Text en Copyright © 2008, American Diabetes Association Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Complications Kim, Young-Hee Kim, Yoon-Sook Park, Chang-Hwan Chung, In-Yong Yoo, Ji-Myong Kim, Jae-Geun Lee, Byung-Ju Kang, Sang-Soo Cho, Gyeong-Jae Choi, Wan-Sung Protein Kinase C-δ Mediates Neuronal Apoptosis in the Retinas of Diabetic Rats via the Akt Signaling Pathway |
title | Protein Kinase C-δ Mediates Neuronal Apoptosis in the Retinas of Diabetic Rats via the Akt Signaling Pathway |
title_full | Protein Kinase C-δ Mediates Neuronal Apoptosis in the Retinas of Diabetic Rats via the Akt Signaling Pathway |
title_fullStr | Protein Kinase C-δ Mediates Neuronal Apoptosis in the Retinas of Diabetic Rats via the Akt Signaling Pathway |
title_full_unstemmed | Protein Kinase C-δ Mediates Neuronal Apoptosis in the Retinas of Diabetic Rats via the Akt Signaling Pathway |
title_short | Protein Kinase C-δ Mediates Neuronal Apoptosis in the Retinas of Diabetic Rats via the Akt Signaling Pathway |
title_sort | protein kinase c-δ mediates neuronal apoptosis in the retinas of diabetic rats via the akt signaling pathway |
topic | Complications |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2494683/ https://www.ncbi.nlm.nih.gov/pubmed/18443201 http://dx.doi.org/10.2337/db07-1431 |
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