Angiotensin II-activated protein kinase D mediates acute aldosterone secretion

The role of protein kinases in the steroidogenic actions of alpha-melanocyte-stimulating hormone (alpha-MSH), angiotensin II (AngII) and corticotropin (ACTH) in the rat adrenal zona glomerulosa was examined. Ro31-8220, a potent selective inhibitor of protein kinase C (PKC), inhibited both AngII- and alpha-MSH-stimulated aldosterone secretion but had no effect on aldosterone secretion in response to ACTH. The effect of Ro31-8220 on PKC activity was measured in subcellular fractions. Basal PKC activity was higher in cytosol than in membrane or nuclear fractions. Incubation of the zona glomerulosa with either alpha-MSH or AngII resulted in significant increases in PKC activity in the nuclear and cytosolic fractions and decreases in the membrane fraction. These effects were all inhibited by Ro31-8220. ACTH caused a significant increase in nuclear PKC activity only, and this was inhibited by Ro31-8220 without any significant effect on the steroidogenic response to ACTH, suggesting that PKC translocation in response to ACTH may be involved in another aspect of adrenal cellular function. Tyrosine phosphorylation has not previously been considered to be an important component of the response of adrenocortical cells to peptide hormones. Both AngII and alpha-MSH were found to activate tyrosine kinase, but ACTH had no effect, observations that have not been previously reported. Tyrphostin 23, a specific antagonist of tyrosine kinases, inhibited aldosterone secretion in response to AngII and alpha-MSH, but not ACTH. These data confirm the importance of PKC in the adrenocortical response to AngII and alpha-MSH, and, furthermore, indicate that tyrosine kinase may play a critical role in the steroidogenic actions of AngII and alpha-MSH in the rat adrenal zona glomerulosa.

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Angiotensin II-Induced Protein Kinase D Activates the ATF/CREB Family of Transcription Factors and Promotes StAR mRNA Expression

Endocrinology ◽

10.1210/en.2013-1485 ◽

2014 ◽

Vol 155 (7) ◽

pp. 2524-2533 ◽

Cited By ~ 12

Author(s):

Lawrence O. Olala ◽

Vivek Choudhary ◽

Maribeth H. Johnson ◽

Wendy B. Bollag

Keyword(s):

Transcription Factors ◽

Angiotensin Ii ◽

Protein Kinase ◽

Mrna Expression ◽

Dominant Negative ◽

Protein Kinase D ◽

Dependent Manner ◽

Aldosterone Production ◽

Glomerulosa Cells ◽

Constitutively Active

Aldosterone synthesis is initiated upon the transport of cholesterol from the outer to the inner mitochondrial membrane, where the cholesterol is hydrolyzed to pregnenolone. This process is the rate-limiting step in acute aldosterone production and is mediated by the steroidogenic acute regulatory (StAR) protein. We have previously shown that angiotensin II (AngII) activation of the serine/threonine protein kinase D (PKD) promotes acute aldosterone production in bovine adrenal glomerulosa cells, but the mechanism remains unclear. Thus, the purpose of this study was to determine the downstream signaling effectors of AngII-stimulated PKD activity. Our results demonstrate that overexpression of the constitutively active serine-to-glutamate PKD mutant enhances, whereas the dominant-negative serine-to-alanine PKD mutant inhibits, AngII-induced StAR mRNA expression relative to the vector control. PKD has been shown to phosphorylate members of the activating transcription factor (ATF)/cAMP response element binding protein (CREB) family of leucine zipper transcription factors, which have been shown previously to bind the StAR proximal promoter and induce StAR mRNA expression. In primary glomerulosa cells, AngII induces ATF-2 and CREB phosphorylation in a time-dependent manner. Furthermore, overexpression of the constitutively active PKD mutant enhances the AngII-elicited phosphorylation of ATF-2 and CREB, and the dominant-negative mutant inhibits this response. Furthermore, the constitutively active PKD mutant increases the binding of phosphorylated CREB to the StAR promoter. Thus, these data provide insight into the previously reported role of PKD in AngII-induced acute aldosterone production, providing a mechanism by which PKD may be mediating steroidogenesis in primary bovine adrenal glomerulosa cells.

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Rapid activation of the novel serine/threonine protein kinase, protein kinase D by phorbol esters, angiotensin II and PDGF-BB in vascular smooth muscle cells

FEBS Letters ◽

10.1016/s0014-5793(98)00427-x ◽

1998 ◽

Vol 427 (2) ◽

pp. 209-212 ◽

Cited By ~ 39

Author(s):

Husna Abedi ◽

Enrique Rozengurt ◽

Ian Zachary

Keyword(s):

Smooth Muscle ◽

Angiotensin Ii ◽

Protein Kinase ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Phorbol Esters ◽

Protein Kinase D ◽

The Novel ◽

Rapid Activation

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A role for phospholipase D in angiotensin II-induced protein kinase D activation in adrenal glomerulosa cell models

Molecular and Cellular Endocrinology ◽

10.1016/j.mce.2012.11.008 ◽

2013 ◽

Vol 366 (1) ◽

pp. 31-37 ◽

Cited By ~ 13

Author(s):

Lawrence O. Olala ◽

Mutsa Seremwe ◽

Ying-Ying Tsai ◽

Wendy B. Bollag

Keyword(s):

Angiotensin Ii ◽

Protein Kinase ◽

Phospholipase D ◽

Protein Kinase D ◽

Cell Models

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Mechanism of inhibitory action of TMB-8 [8-(NN-diethylamino)octyl-3,4,5-trimethoxybenzoate] on aldosterone secretion in adrenal glomerulosa cells

Biochemical Journal ◽

10.1042/bj2320087 ◽

1985 ◽

Vol 232 (1) ◽

pp. 87-92 ◽

Cited By ~ 39

Author(s):

I Kojima ◽

K Kojima ◽

H Rasmussen

Keyword(s):

Protein Kinase C ◽

Angiotensin Ii ◽

Protein Kinase ◽

Calcium Release ◽

Calcium Influx ◽

Inhibitory Effect ◽

Dependent Manner ◽

Aldosterone Secretion ◽

Kinase C ◽

Glomerulosa Cells

The mechanism of 8-(NN-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) action was evaluated in isolated adrenal glomerulosa cells. TMB-8 inhibits both angiotensin II- and K+-stimulated aldosterone secretion in a dose-dependent manner. The ID50 for angiotensin II- and K+-stimulated aldosterone secretion is 46 and 28 microM, respectively. In spite of the fact that 100 microM-TMB-8 inhibits angiotensin II-stimulated aldosterone secretion almost completely, TMB-8 (100 microM) does not inhibit angiotensin II-induced 45Ca2+ efflux from prelabelled cells nor does it affect inositol 1,4,5-trisphosphate-induced calcium release from non-mitochondrial pool(s) in saponin-permeabilized cells. TMB-8 has no inhibitory effect on A23187-induced aldosterone secretion, but 12-O-tetradecanoylphorbol 13-acetate-induced aldosterone secretion is completely abolished. TMB-8 effectively inhibits both angiotensin II- and K+-induced increases in calcium influx but has no effect on A23187-induced calcium influx. TMB-8 inhibits the activity of protein kinase C dose-dependently. These results indicate that TMB-8 inhibits aldosterone secretion without inhibiting mobilization of calcium from an intracellular pool. The inhibitory effect of TMB-8 is due largely to an inhibition of plasma membrane calcium influx, but this drug also inhibits the activity of protein kinase C directly.

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