Possible role for mitochondrial calcium in angiotensin II- and potassium-stimulated steroidogenesis in bovine adrenal glomerulosa cells.

Abstract

In adrenal zona glomerulosa cells, the action of angiotensin

Submitochondrial Distribution of Three Key Steroidogenic Proteins (Steroidogenic Acute Regulatory Protein and Cytochrome P450scc and 3β-Hydroxysteroid Dehydrogenase Isomerase Enzymes) upon Stimulation by Intracellular Calcium in Adrenal Glomerulosa Cells

“…Our current model of the mechanisms of calcium-induced activation of steroidogenesis would favor a dual site of action for Ca 2ϩ : in addition to an obligatory role for Ca 2ϩ influx into the mitochondria, as demonstrated previously in permeabilized glomerulosa cells (45) and in glomerulosa cells treated with a blocker of the mitochondrial Na ϩ /Ca 2ϩ exchanger (25), the present cycloheximide results imply an effect of cytosolic Ca 2ϩ on StAR protein expression.…”

“…Both Ang II and K ϩ elicit sustained changes in mitochondrial free calcium concentration (25). However, the precise site(s) of action of Ca 2ϩ responsible for this increased pregnenolone formation remained to be determined.…”

Calcium-dependent mitochondrial cAMP production enhances aldosterone secretion

“…More specifically, we here demonstrate that: i) angiotensin II, an agonist known to induce (often oscillatory) increases in cytosolic and mitochondrial Ca 2+ (Brandenburger et al, 1996;Lalevee et al, 2003;Spät and Hunyady, 2004;Spät and Pitter, 2004), as well as reduction in pyridine nucleotides (Pralong et al, 1992;Pralong et al, 1994;Rohács et al, 1997), also causes a dose dependent rise in mt-cAMP; ii) the effects of angiotensin II on mt-cAMP are reduced by buffering matrix Ca 2+ increases caused by the expression of mitoS100G (Wiederkehr et al, 2011), by siRNA reduction in sAC expression or by the sAC inhibitor 2-OHE and are augmented by the PDE2A inhibitor EHNA; iii) a clear increase in mt-cAMP is also caused by the well known sAC activator, bicarbonate (Buck et al, 1999;Jaiswal and Conti, 2003;Litvin et al, 2003;Steegborn et al, 2005b). Three lines of evidence support the conclusion that sAC is primarily localized in the mitochondria: i) the majority of the protein band (molecular weight 50 kDa), revealed in lysates of H295R cells by immunoblotting with anti-sAC antibodies and corresponding to the truncated, fully active form of sAC (Buck et al, 1999), remained in the pellet after plasma membrane permeabilization with digitonin; ii) the mitochondrial cAMP sensor 4mtH30 and the cytosolic sensor H30 responded with opposite signals to bicarbonate addition, i.e.…”

Mitochondrial Ca2+ as a key regulator of cell life and death

“…The two examples best studied are the endocrine pancreas, where mitochondrial Ca 2 þ modulates insulin secretion, 32 and the granulosa cells of the adrenal gland, where it controls a key step in aldosterone synthesis. 33 A schematic view of mitochondrial Ca 2 þ regulation and of the physiological processes that are modulated is presented in Figure 2.…”