TY - JOUR
T1 - Up-regulation of genes for oxidative phosphorylation and protein turnover in diabetic mouse retina
AU - Adachi-Uehara, Nanami
AU - Kato, Masaki
AU - Nimura, Yoshinori
AU - Seki, Naohiko
AU - Ishihara, Akinori
AU - Matsumoto, Eriko
AU - Iwase, Katsuro
AU - Ohtsuka, Satoko
AU - Kodama, Hiroki
AU - Mizota, Atsushi
AU - Yamamoto, Shuichi
AU - Adachi-Usami, Emiko
AU - Takiguchi, Masaki
N1 - Funding Information:
We are grateful to T. Hiwasa, N. Fujimoto, and our colleagues for suggestions, help, and discussions. This work was supported in part by Grants-in-Aid from the Ministry of Education, Culture, Science, Sports and Technology of Japan.
PY - 2006/10
Y1 - 2006/10
N2 - Diabetic retinopathy is one of the most frequent complications of diabetes and is a leading cause of vision loss in adulthood. To better understand the molecular pathophysiology of diabetic retinopathy, we performed comprehensive gene expression analysis of the mouse retina under diabetic conditions with an in-house cDNA microarray system that was designed to be suitable for the small amount of RNA available from a single mouse retina. Diabetes was induced in male C57BL/6 mice by an intraperitoneal injection of streptozotocin, and the changes in retinal mRNA levels were examined in three pairs of diabetic and age-matched control mice at 1 and 3 months after the injection of streptozotocin. Northern blot analysis with amplified total cRNA confirmed the increase in mRNA levels of several selected genes. Most of the significantly up-regulated genes could be classified into two functional categories: oxidative phosphorylation and protein turnover. All mitochondrial DNA-encoded and most of the nuclear DNA-encoded genes for oxidative phosphorylation were up-regulated in the diabetic retina. This was in sharp contrast with a previous report of a down-regulation of these genes in skeletal muscles of streptozotocin-induced diabetic mice and type 2 diabetic humans. Genes for protein synthesis and ubiquitin were also up-regulated in the diabetic retina, suggesting the increase in turnover rates for at least a part of the protein population. Taken together, the diabetic retina appears to be in a state activated for intermediary metabolism, presumably because of an increase in insulin-independent glucose influx. These results provide insights into possible preventive and therapeutic intervention of diabetic retinopathy.
AB - Diabetic retinopathy is one of the most frequent complications of diabetes and is a leading cause of vision loss in adulthood. To better understand the molecular pathophysiology of diabetic retinopathy, we performed comprehensive gene expression analysis of the mouse retina under diabetic conditions with an in-house cDNA microarray system that was designed to be suitable for the small amount of RNA available from a single mouse retina. Diabetes was induced in male C57BL/6 mice by an intraperitoneal injection of streptozotocin, and the changes in retinal mRNA levels were examined in three pairs of diabetic and age-matched control mice at 1 and 3 months after the injection of streptozotocin. Northern blot analysis with amplified total cRNA confirmed the increase in mRNA levels of several selected genes. Most of the significantly up-regulated genes could be classified into two functional categories: oxidative phosphorylation and protein turnover. All mitochondrial DNA-encoded and most of the nuclear DNA-encoded genes for oxidative phosphorylation were up-regulated in the diabetic retina. This was in sharp contrast with a previous report of a down-regulation of these genes in skeletal muscles of streptozotocin-induced diabetic mice and type 2 diabetic humans. Genes for protein synthesis and ubiquitin were also up-regulated in the diabetic retina, suggesting the increase in turnover rates for at least a part of the protein population. Taken together, the diabetic retina appears to be in a state activated for intermediary metabolism, presumably because of an increase in insulin-independent glucose influx. These results provide insights into possible preventive and therapeutic intervention of diabetic retinopathy.
KW - diabetic retinopathy
KW - microarray
KW - mitochondria
KW - retina
KW - ubiquitin
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U2 - 10.1016/j.exer.2006.04.012
DO - 10.1016/j.exer.2006.04.012
M3 - Article
C2 - 16780836
AN - SCOPUS:33747887337
VL - 83
SP - 849
EP - 857
JO - Experimental Eye Research
JF - Experimental Eye Research
SN - 0014-4835
IS - 4
ER -