Angiotensin II activates Akt/protein kinase B by an arachidonic acid/redox-dependent pathway and independent of phosphoinositide 3-kinase.
Angiotensin II (Ang II) exerts contractile and trophic effects in glomerular mesangial cells (MCs). One potential downstream target of Ang II is the protein kinase Akt/protein kinase B ( PKB). We investigated the effect of Ang II on Akt/ PKB activity in MCs. Ang II causes rapid activation of Akt/ PKB (5-10 min) but delayed activation of phosphoinositide 3-kinase ( PI3-K) (30 min). Activation of Akt/ PKB by Ang II was not abrogated by the PI3-K inhibitors or by the introduction of a dominant negative PI3-K, indicating that in MCs, PI3-K is not an upstream mediator of Akt/ PKB activation by Ang II. Incubation of MCs with phospholipase A2 inhibitors also blocked Akt/ PKB activation by Ang II. AA mimicked the effect of Ang II. Inhibitors of cyclooxygenase-, lipoxyogenase-, and cytochrome P450-dependent metabolism did not influence AA-induced Akt/ PKB activation. However, the antioxidants N-acetylcysteine and diphenylene iodonium inhibited both AA- and Ang II-induced Akt/ PKB activation. Dominant negative mutant of Akt/ PKB or antioxidants, but not the dominant negative form of PI3-K, inhibited Ang II-induced protein synthesis and cell hypertrophy. These data provide the first evidence that Ang II induces protein synthesis and hypertrophy in MCs through AA/redox-dependent pathway and Akt/ PKB activation independent of PI3-K.[1]References
- Angiotensin II activates Akt/protein kinase B by an arachidonic acid/redox-dependent pathway and independent of phosphoinositide 3-kinase. Gorin, Y., Kim, N.H., Feliers, D., Bhandari, B., Choudhury, G.G., Abboud, H.E. FASEB J. (2001) [Pubmed]
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