Up-regulation of genes for oxidative phosphorylation and protein turnover in diabetic mouse retina.
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.
Adachi-Uehara
Nanami
N
Department of Biochemistry and Genetics, Chiba University Graduate School of Medicine, Inohama 1-8-1, Chiba 260-8670, Japan.
Kato
Masaki
M
Nimura
Yoshinori
Y
Seki
Naohiko
N
Ishihara
Akinori
A
Matsumoto
Eriko
E
Iwase
Katsuro
K
Ohtsuka
Satoko
S
Kodama
Hiroki
H
Mizota
Atsushi
A
Yamamoto
Shuichi
S
Adachi-Usami
Emiko
E
Takiguchi
Masaki
M
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000378:metabolism*; D005136:Eye Proteins / Q000096:biosynthesis* / Q000235:genetics; D015723:Gene Library; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010085:Oxidative Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D012160:Retina / Q000378:metabolism*; D025801:Ubiquitin / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation
D005136:Eye Proteins; D012333:RNA, Messenger; D025801:Ubiquitin