A 90-kD Na(+)-H+ exchanger kinase has increased activity in spontaneously hypertensive rat vascular smooth muscle cells

Hypertension
V N PhanB C Berk

Abstract

Increased activity of the Na(+)-H+ exchanger (NHE-1 isoform) has been observed in cells and tissues from hypertensive humans and animals, including the spontaneously hypertensive rat (SHR). No mutation in NHE-1 DNA sequence or alteration in NHE-1 mRNA and protein expression has been demonstrated in hypertension, indicating that alterations in proteins that regulate NHE-1 activity are responsible for increased activity. The recent finding that NHE-1 phosphorylation in SHR vascular smooth muscle cells (VSMCs) was greater than in Wistar-Kyoto rat (WKY) VSMCs suggested that NHE-1 kinases may represent an abnormal regulatory pathway present in hypertension. To define NHE-1 kinases altered in the hypertensive phenotype. We measured NHE-1 kinase activity by an in-gel-kinase assay using a recombinant glutathione S-transferase NHE-1 fusion protein as a substrate. At least 7 NHE-1 kinases (42 to 90 kD) were present in VSMCs. We studied a 90-kD kinase because it was the major NHE-1 kinase and exhibited differences between SHR and WKY. Comparison of 90-kD kinase activity revealed that SHR VSMCs had increased activity in growth-arrested cells and in cells stimulated by angiotensin II (100 nmol/L for 5 minutes). Activation of the 90-kD kinas...Continue Reading

References

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Citations

Sep 21, 2011·The Journal of Biological Chemistry·Stefan KösterÖzkan Yildiz
Nov 21, 2002·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Emily Slepkov, Larry Fliegel
Jan 28, 2005·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Larry Fliegel, Morris Karmazyn
Jun 29, 2000·Annual Review of Biochemistry·D L Garbers, S K Dubois
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Jul 23, 2014·BioMed Research International·Christopher T ChanGrant R Drummond
Sep 19, 2006·Metabolism: Clinical and Experimental·Sofia G TsouliMoses S Elisaf
Nov 6, 2003·The Journal of Biological Chemistry·Yurii V MukhinJohn R Raymond
Jan 16, 2007·Canadian Journal of Physiology and Pharmacology·Mackenzie E Malo, Larry Fliegel
Dec 22, 1999·The American Journal of Physiology·R S HaworthM Avkiran
Jan 15, 2000·The Journal of Biological Chemistry·J AbeB C Berk
Jul 19, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Emily C RothsteinPamela A Lucchesi
Dec 10, 2008·Expert Opinion on Therapeutic Targets·Larry Fliegel

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