Endothelin-1 activation of JAK2 in vascular smooth muscle cells involves NAD(P)H oxidase-derived reactive oxygen species

Amy K.L. Banes-Berceli, Safia Ogbi, Amany Tawfik, Bela Patel, Amanda Shirley, David M. Pollock, David Fulton, Mario B. Marrero

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Endothelin-1 (ET-1) and JAK2 are both implicated in diabetic complications. Therefore, we investigated whether ET-1 differentially actives JAK2 under conditions of normal (5 mM) and high (25 mM) glucose. We tested the hypothesis that reactive oxygen species mediate the activation of JAK2 in response to ET-1. In rat aortic vascular smooth muscle cells (VSMC), ET-1 (10-7 M, 5 min) stimulated the activation of JAK2, which was further enhanced under high glucose conditions. Allopurinol (xanthine oxidase inhibitor, 1 μM) and l-NAME (nitric oxide synthase inhibitor, 1 mM) had no effect on ET-1-induced JAK2 activation, while apocynin (NAD(P)H oxidase inhibitor 100 μM) resulted in a significant inhibition of ET-1-induced JAK2 and MAPK activation. Overexpression of SOD did not inhibit ET-1-induced activation of JAK2, but catalase (50 units/mL) treatment resulted in complete inhibition. In vivo administration of apocynin (1.5 mM) resulted in a significant decrease (∼ 50%), while the ETA receptor antagonist ABT-627 completely inhibited phosphorylation of JAK2 in aortae from STZ-induced diabetic rats. Additionally, DHE staining of aortic sections was significantly reduced in diabetic rats treated with ABT-627. These data suggest that in VSMC, ET-1 via the ETA receptor, utilizes NAD(P)H oxidase to activate JAK2.

Original languageEnglish (US)
Pages (from-to)310-319
Number of pages10
JournalVascular Pharmacology
Issue number5
StatePublished - Nov 2005


  • Diabetes
  • Endothelin-1
  • Reactive oxygen species
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Physiology
  • Molecular Medicine
  • Pharmacology


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