title: Streptozotocin-induced diabetes affects in rat liver citrate carrier gene expression by transcriptional and posttranscriptional mechanisms.
abstract: Citrate carrier (CiC), also known as tricarboxylate carrier, is an integral protein of the mitochondrial inner membrane. It is an essential component of the shuttle system by which mitochondrial acetyl-CoA, primer for both fatty acid and cholesterol synthesis, is transported into the cytosol, where lipogenesis occurs. Here, we report the effect of streptozotocin-induced diabetes on the activity and expression of CiC in rat liver mitochondria. A significant reduction of CiC activity and a parallel decline in the abundance of CiC mRNA were found in liver from diabetic rats. Diabetes did not influence CiC mRNA stability, whereas nuclear run-on assay revealed that the transcriptional rate of CiC mRNA decreased, when compared to control, in the nuclei from diabetic rats. The ratio of mature to precursor CiC RNA decreased in diabetic animals, indicating that the splicing of CiC RNA was also affected. The 3'-end processing rate of CiC mRNA was not altered in diabetes. These results suggest that diabetes affects CiC expression at both transcriptional and posttranscriptional levels. In addition, by in vitro transfection experiments in rat hepatocytes cultured in the absence of insulin, a reduction of CiC promoter activity was observed, and this was ascribed to a decreased expression of sterol regulatory element-binding protein-1 transcriptional factor. Furthermore, the binding of sterol regulatory element-binding protein-1 to the CiC promoter was reduced in STZ-diabetic rats with respect to control ones, and it was restored to the control values after insulin treatment.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Department of Biological and Environmental Sciences and Technologies, University of Salento, Via Prov. Lecce-Monteroni, 73100 Lecce, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Damiano
authors.forename: Elisa
authors.initials: E
authors.lastname: Mercuri
authors.forename: Eleonora
authors.initials: E
authors.lastname: Stanca
authors.forename: Gabriele Vincenzo
authors.initials: GV
authors.lastname: Gnoni
authors.forename: Luisa
authors.initials: L
authors.lastname: Siculella
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012326:RNA Splicing; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D007328:Insulin; D012322:RNA Precursors; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; C020723:citrate-binding transport protein; D000105:Acetyl Coenzyme A