Interleukin-1 inhibits angiotensin II-stimulated protein kinase B pathway in renal mesangial cells via the inducible nitric oxide synthase

Rölz, W.; Xin, C.; Ren, S.; Pfeilschifter, J.; Huwiler, A.

European Journal of Pharmacology 442(3): 195-203


ISSN/ISBN: 0014-2999
PMID: 12065072
DOI: 10.1016/s0014-2999(02)01545-5
Accession: 010867098

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Exposure of rat renal mesangial cells to angiotensin II and angiotensin III leads to a rapid phosphorylation and activation of the protein kinase B (PKB) pathway. The angiotensin II analogs angiotensin-(1-7), angiotensin-(1-6) and angiotensin-(3-8) were unable to activate PKB. The angiotensin II and III effects are mediated by the angiotensin type 1 receptor as documented by the inhibitory action of valsartan. Furthermore, angiotensin II-induced activation of PKB involves neither a pertussis toxin-sensitive pathway nor the small G proteins of the Rho/Rac/cdc42 family, but is completely blocked by inhibitors of the PI 3-kinase. Moreover, angiotensin II-stimulated PKB activation is inhibited by long-term pretreatment with interleukin-1 beta, an effect that is reversed by the NO synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA). Similarly, the nitric oxide donor (Z)-1-[2-Aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (Deta-NO) blocks the angiotensin II-induced PKB activation. The NO-mediated inhibition of PKB activation in turn is reversed by the phosphatase inhibitor calyculin A but not by ocadaic acid, implying the induction of a protein phosphatase 1 activity by NO.