Different localization in rat brain of the novel cytosolic ketone body-utilizing enzyme, acetoacetyl-CoA synthetase, as compared to succinyl-CoA:3-oxoacid CoA-transferase.
In lipogenic tissue cytosol, ketone bodies are known to be activated by acetoacetyl-CoA synthetase (AACS) and incorporated into cholesterol and fatty acids. In order to investigate the physiological role of AACS in the brain, we examined the localization of AACS mRNA in rat brain by in situ hybridization using a labeled probe. High labeling was observed in the midbrain, pons/medulla, cerebral cortex, hippocampus and cerebellum, and the localization profile of AACS mRNA was different from that of succinyl-CoA:3-oxoacid CoA-transferase (SCOT), a mitochondrial ketone body-activating enzyme. In addition, the expression of AACS mRNA in the cerebellum was restricted primarily to glial cells, while in the cerebral cortex, it was restricted to neuronal cells. Streptozotocin treatment caused remarkable decreases in AACS mRNA levels in all regions where expression was observed, but changes in SCOT mRNA levels were not observed. These results suggest that the physiological role of AACS is different from that of SCOT and varies depending upon its localization in the brain.
Department of Health Chemistry, Faculty of Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-Chome, Shinagawa-ku, Tokyo 142-8501, Japan.
Mizuomi
M
Ohnuki
Noriko
N
Takahashi
Masahiro
M
Yamasaki
Tetsuya
T
Fukui
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D015152:Blotting, Northern; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D003066:Coenzyme A Ligases / Q000235:genetics*; D015256:Coenzyme A-Transferases / Q000235:genetics*; D003600:Cytosol / Q000201:enzymology; D018076:DNA, Complementary; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D017403:In Situ Hybridization; D007657:Ketone Bodies / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000494:pharmacology; D014018:Tissue Distribution
D000903:Antibiotics, Antineoplastic; D018076:DNA, Complementary; D007657:Ketone Bodies; D012333:RNA, Messenger; D013311:Streptozocin; D015256:Coenzyme A-Transferases; C021460:3-ketoacid CoA-transferase; D003066:Coenzyme A Ligases; C023747:acetoacetyl-CoA synthetase