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Expression of NG,NG...
Expression of NG,NG-dimethylarginine dimethylaminohydrolase and protein arginine N-methyltransferase isoforms in diabetic rat kidney: effects of angiotensin II receptor blockers
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- Onozato, Maristela L (författare)
- University of Tokyo, Japan and Georgetown University, USA
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- Tojo, Akihiro (författare)
- University of Tokyo, Japan
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- Leiper, James (författare)
- University College London, UK
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- Fujita, Toshiro (författare)
- University of Tokyo, Japan
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- Palm, Fredrik (författare)
- Uppsala universitet,Institutionen för medicinsk cellbiologi,Division of Nephrology and Hypertension, Cardiovascular Kidney Hypertension Institutet, Georgetown University, USA
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- Wilcox, Christopher S (författare)
- Georgetown University, USA
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(creator_code:org_t)
- American Diabetes Association, 2008
- 2008
- Engelska.
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 57:1, s. 172-180
- Relaterad länk:
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http://www.ncbi.nlm....
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http://diabetes.diab...
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https://urn.kb.se/re...
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https://doi.org/10.2...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Objective: The nitric oxide (NO) synthase inhibitor, asymmetric dimethylarginine (ADMA) is generated by protein arginine N-methyltransferase (PRMT)-1 and is metabolized by NG, NG-dimethylarginine dimethylaminohydrolase (DDAH). We tested the hypothesis that increased serum ADMA (SADMA) in the streptozotocin (STZ)-induced rat model of diabetes mellitus (DM) is mediated by an angiotensin receptor blocker– sensitive change in DDAH or PRMT expression.Research design and Methods: Data were compared from 4 groups of rats: sham injected controls; untreated STZ- DM at 4 weeks; STZ-DM rats administered the angiotensin II receptor blocker telmisartan for 2 weeks; control rats administered telmisartan for 2 weeks.Results: Immunostaining and Western blotting of microdissected nephron segments localized DDAH I in the proximal tubules and DDAH II in the glomeruli, afferent arterioles, macula densa and distal nephron. Renal angiotensin II and SADMA increased with DM but were normalized by 2 weeks of telmisartan. DDAH I expression was decreased in DM kidneys while DDAH II expression was increased. These changes were reversed by telmisartan which also reduced expression of PRMT-1 and -5. Telmisartan increased expressions of DDAH I but decreased DDAH II in Ang II-stimulated kidney slices ex-vivo.Conclusion: Renal angiotensin II and SADMA are increased in insulinopenic DM. They are normalized by an angiotensin II receptor blocker which increases the renal expression of DDAH I, decreases PRMT-1 and increases renal NO metabolites.
Nyckelord
- MEDICINE
- MEDICIN
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- art (ämneskategori)
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