{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:52:04Z","timestamp":1787025124581,"version":"build-2736575974"},"reference-count":36,"publisher":"American Diabetes Association","issue":"8","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,8,1]]},"abstract":"<jats:p>OBJECTIVE\u2014Protein kinase C (PKC)-\u03b4, an upstream regulator of the Akt survival pathway, contributes to cellular dysfunction in the pathogenesis of diabetes. Herein, we examined the role of PKC-\u03b4 in neuronal apoptosis through Akt in the retinas of diabetic rats.<\/jats:p>\n                  <jats:p>RESEARCH DESIGN AND METHODS\u2014We 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-\u03b4 affects Akt signaling and cell death in OLETF rat retinas, we examined 1) PKC-\u03b4 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-\u03b4 inhibitor, or small interfering RNAs (siRNAs) for PKC-\u03b4 and HSP90.<\/jats:p>\n                  <jats:p>RESULTS\u2014In OLETF retinas from 35-week-old rats, ganglion cell death, PKC-\u03b4 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-\u03b4 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.<\/jats:p>\n                  <jats:p>CONCLUSIONS\u2014PKC-\u03b4 activation contributes to neuro-retinal apoptosis in diabetic rats by inhibiting Akt-mediated signaling pathways.<\/jats:p>","DOI":"10.2337\/db07-1431","type":"journal-article","created":{"date-parts":[[2008,4,28]],"date-time":"2008-04-28T20:55:28Z","timestamp":1209416128000},"page":"2181-2190","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":37,"title":["Protein Kinase C-\u03b4 Mediates Neuronal Apoptosis in the Retinas of Diabetic Rats via the Akt Signaling Pathway"],"prefix":"10.2337","volume":"57","author":[{"given":"Young-Hee","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Anatomy and Neurobiology, School of Medicine, Institute of Health Science, Gyeongsang National University, Jinju, Gyeongnam, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon-Sook","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, School of Medicine, Institute of Health Science, Gyeongsang National University, Jinju, Gyeongnam, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Hwan","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, School of Medicine, Institute of Health Science, Gyeongsang National University, Jinju, Gyeongnam, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In-Yong","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, Institute of Health Science, Gyeongsang National University, Jinju, Gyeongnam, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Myong","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, Institute of Health Science, Gyeongsang National University, Jinju, Gyeongnam, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Geun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung-Ju","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Soo","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, School of Medicine, Institute of Health Science, Gyeongsang National University, Jinju, Gyeongnam, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyeong-Jae","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, School of Medicine, Institute of Health Science, Gyeongsang National University, Jinju, Gyeongnam, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Sung","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, School of Medicine, Institute of Health Science, Gyeongsang National University, Jinju, Gyeongnam, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031208001051000_R1","doi-asserted-by":"crossref","unstructured":"Okhrimenko H, Lu W, Xiang C, Hamburger N, Kazimirsky G, Brodie C: Protein kinase C-epsilon regulates the apoptosis and survival of glioma cells. 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