A role for protein kinase C‐ϵ in angiotensin II stimulation of phospholipase D in rat renal mesangial cells

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Abstract
The role of Ca2+ and protein kinase C (PKC) in the regulation of phosphatidylcholine‐hydrolyzing phospholipase D (PLD) was investigated in angiotensin II‐stimulated mesangial cells. Elevation of cytosolic free Ca2+ by the calcium ionophore, A23187, or the Ca2+‐ATPase inhibitor, thapsigargin, slightly increased PLD‐stimulated phosphatidylethanol formation. However, chelation of cytosolic Ca2+ with high concentrations of quin 2 did not attenuate angiotensin II‐indueed phosphatidylethanol production, thus suggesting that Ca2+ is not crucially involved in agonist‐stimulated PLD activation. Stimulation of PKC by phorbol esters increased PLD activity in mesangial cells. Down‐regulation of PKC‐α and ‐δ isoenzymes by 8 h phorbol ester treatment still resulted in full PLD activation. In contrast, a 24 h treatment of mesangial cells with phorbol ester, a regimen that also causes depletion of PKC‐ϵ, abolished angiotensin II‐evoked phosphatidylethanol formation. In addition, the selective PKC inhibitor, calphostin C, attenuated hormone‐induced PLD activity. In summary, these data suggest that angiotensin II stimulation of phospholipase D appears to involve the PKC‐ϵ isoenzyme, activated by DAG derived from phosphoinositide hydrolysis.

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