Diabetes-induced up-regulation of uncoupling protein-2 results in increased mitochondrial uncoupling in kidney proximal tubular cells
2008 (English)In: Biochimica et Biophysica Acta, ISSN 0006-3002, Vol. 1777, no 7-8, 935-940 p.Article in journal (Refereed) Published
We have previously reported increased O(2) consumption unrelated to active transport by tubular cells and up-regulated mitochondrial uncoupling protein (UCP)-2 expressions in diabetic kidneys. It is presently unknown if the increased UCP-2 levels in the diabetic kidney results in mitochondrial uncoupling and increased O(2) consumption, which we therefore investigated in this study. The presence of UCP-2 in proximal tubular cells was confirmed by immunohistochemistry and found to be increased (western blot) in homogenized tissue and isolated mitochondria from kidney cortex of diabetic rats. Isolated proximal tubular cells had increased total and ouabain-insensitive O(2) consumption compared to controls. Isolated mitochondria from diabetic animals displayed increased glutamate-stimulated O(2) consumption (in the absence of ADP and during inhibition of the ATP-synthase by oligomycin) compared to controls. Guanosine diphosphate, an UCP inhibitor, and bovine serum albumin which removes fatty acids that are essential for UCP-2 uncoupling activity, independently prevented the increased glutamate-stimulated O(2) consumption in mitochondria from diabetic animals. In conclusion, diabetic rats have increased mitochondrial UCP-2 expression in renal proximal tubular cells, which results in mitochondrial uncoupling and increased O(2) consumption. This mechanism may be protective against diabetes-induced oxidative stress, but will increase O(2) usage. The subsequently reduced O(2) availability may contribute to diabetes-induced progressive kidney damage.
Place, publisher, year, edition, pages
2008. Vol. 1777, no 7-8, 935-940 p.
Diabetes mellitus, kidney, mitochondria, uncoupling protein-2, oxygen consumption
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-99304DOI: 10.1016/j.bbabio.2008.03.030ISI: 000257696400054PubMedID: 18439413OAI: oai:DiVA.org:liu-99304DiVA: diva2:657209
Conference Information: 15th European Bioenergetic ConferenceTrinity Coll, Dublin, IRELAND, JUL 19-24, 20082009-11-042013-10-152013-10-18