Janus Kinase 2 and Calcium Are Required for Angiotensin II-dependent Activation of Steroidogenic Acute Regulatory Protein Transcription in H295R Human Adrenocortical Cells

Li, Jianghong; Feltzer, Rhona; Dawson, Kevin L.; Hudson, Elizabeth; Clark, Barbara J.

doi:10.1074/jbc.m305232200

Cited by 36 publications

(23 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Surprisingly, analysis of corticosterone production by isolated adrenal cells provided clear evidence that unlike PRL, JAK2 was involved in basal and ACTH-induced steroidogenesis. Previous data have already reported an early role of JAK2 in the mediation of hormone effects through action on G proteincoupled receptors including angiotensin receptor AGTR 1a in adrenocortical cells (19) or LH receptor LHCGR in ovarian cells (30). In follicular cells, JAK2 tyrosine phosphorylation was increased in response to LH.…”

Section: Discussionmentioning

confidence: 99%

“…This effect of JAK2 is in part mediated through the MAPK/ERK1/2 pathway (19,33) even though the molecular target of JAK2 was not clearly identified in adrenal cells. Our data rather support the finding that in adrenocortical cells, activated JAK2 levels are not sensitive to ACTH.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, JAK2 was shown to be involved in the angiotensin-dependent stimulation of Star transcription and progesterone production in the H295R cell line. However the molecular targets of JAK2 remained unidentified in this process (19). More recently, bromocriptine-induced hypoprolactinemia was shown to decrease the stressed induced STAT5 phosphorylation in adrenal gland in Hatano high avoidance rats that display hyperreactivity to stress.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Transcriptional Control of Adrenal Steroidogenesis

Lefrançois‐Martinez

Blondet-Trichard

Binart

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

In the adrenal gland, adrenocorticotropin (ACTH) acting through the cAMP protein kinase (PKA) transduction pathway is the main regulator of genes involved in glucocorticoid synthesis. The prolactin (PRL) receptor is expressed in the adrenal cortex of most mammals, but experimental proof that PRL ensures direct control on glucocorticoid synthesis in rodents remains elusive. To unravel the physiological importance of PRL in adrenocortical functions, we measured steroidogenic capacity of Prlr-deficient mice (Prlr ؊/؊ ) and explored the influence of JAK/STAT signaling, the major PRL transduction pathway, on the steroidogenic activity of adrenocortical cell cultures. We demonstrate that lack of Prlr does not affect basal (nor stress-induced) corticosterone levels in mice. PRL triggers JAK2/STAT5-dependent transcription in adrenal cells, but this does not influence corticosterone release. In contrast, pharmacological or siRNA-mediated inhibition of JAK2 reveals its essential role in both basal and ACTH/cAMP-induced steroidogenesis. We demonstrate that nuclear JAK2 regulates the amount of active transcription factor CREB (cAMP response element-binding protein) through tyrosine phosphorylation and prevention of proteasomal degradation, which in turn leads to transcriptional activation of the rate-limiting steroidogenic Star gene. Hence, we describe a novel link between PKA and JAK2 by which nuclear JAK2 signaling controls adrenal steroidogenesis by increasing the stability of CREB.Acute and chronic adrenal cortex steroidogenesis is regulated mainly through the adrenocorticotropin (ACTH) activation of the cAMP-dependent protein kinase A (PKA) signaling pathway. Chronic response to ACTH results in increased transcription of genes encoding steroidogenic enzymes and the proteins responsible for cholesterol mobilization and transport, such as the steroidogenic acute regulatory protein (STAR), 4 which mediates the rate-limiting and regulated step in steroidogenesis. cAMP-induced PKA activations result at least in the phosphorylation of the transcription factors GATA-4-binding protein, steroidogenic factor 1 (SF1), CAAT enhancerbinding protein (C/EBP) and cAMP response element-binding protein (CREB). These in turn stimulate transcription of genes involved in steroidogenesis (1, 2). The cAMP-responsive unit of the mouse Star proximal promoter (Ϫ110 and Ϫ67 bp) is a prototypical sequence that involves multiple DNA binding motifs for these transcription factors including three CRE halfsites that can bind CREB (2-4).Although cAMP is an essential inducer of steroidogenesis, other mechanisms triggered by paracrine and endocrine signals have been involved in the regulation of steroid synthesis in basal or stress-induced conditions. They can either act independently or in synergy with the PKA signaling (5). Prolactin (PRL) is a stress-related protein that has been reported to enhance aldosterone and glucocorticoid production in various mammalian species including rat, guinea pig, mouse, pig, and human (6 -12). A direct action of PRL o...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Transcriptional Control of Adrenal Steroidogenesis

Lefrançois‐Martinez

Blondet-Trichard

Binart

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Moreover, CTRP1 did not increase the transcription of CYP11B1, the enzyme responsible for glucocorticoid synthesis. Previous reports found that Ang II increased the transcription of CYP11B1 and STAR (Li et al 2003, Romero et al 2004, and AT 1 R blockade had no effect, suggesting that this aldosterone secretion induced by CTRP-1 is independent of Ang II-mediated regulation mechanism (Jeon et al 2008).…”

Section: Ctrp-1 Complement-c1qmentioning

confidence: 99%

Adipocytes, aldosterone and obesity-related hypertension

Cat¹,

Friederich‐Persson²,

White³

et al. 2016

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Aldosterone and obesity a nguyen dinh cat and others 57:1 F7-F21 AbstractUnderstanding the mechanisms linking obesity with hypertension is important in the current obesity epidemic as it may improve therapeutic interventions. Plasma aldosterone levels are positively correlated with body mass index and weight loss in obese patients is reported to be accompanied by decreased aldosterone levels. This suggests a relationship between adipose tissue and the production/secretion of aldosterone. Aldosterone is synthesized principally by the adrenal glands, but its production may be regulated by many factors, including factors secreted by adipocytes. In addition, studies have reported local synthesis of aldosterone in extra-adrenal tissues, including adipose tissue. Experimental studies have highlighted a role for adipocyte-secreted aldosterone in the pathogenesis of obesity-related cardiovascular complications via the mineralocorticoid receptor. This review focuses on how aldosterone secretion may be influenced by adipose tissue and the importance of these mechanisms in the context of obesity-related hypertension.

show abstract

“…ERK1/2 are phosphorylated and activated by MEK1/2 (for review see Spät & Hunyady 2004). In aldosterone producing cells, Ang II was reported to activate the ERK, JNK and p38 MAPK pathways (Watanabe et al 1996, McNeill et al 1998, Tian et al 1998, Natarajan et al 2002, Gu et al 2003, Li et al 2003. Also, Ang II activated p42 MAPK via protein kinase C in bovine adrenal glomerulosa cells (Tian et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Novel protein kinase C-epsilon inhibits human CYP11B2 gene expression through ERK1/2 signalling pathway and JunB

Lehoux

Lefèbvre²

2006

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

We previously reported that H295R cells co-express three diacylglycerol (DAG)-dependent protein kinase Cs (PKCs), namely conventional (c) PKC and novel (n) PKC´and PKCq. The aim of the present work was to evaluate the implication of DAG-dependent PKCs in the activation of p44/42 MAP kinase (MAPK) by angiotensin II (Ang II) and to define the role of this pathway towards CYP11B2 regulation in H295R cells. The PKC inhibitor bisindolylmaleimide 1 (Bis) inhibited Ang II-induced p44/42 MAPK phosphorylation whereas the cPKC inhibitor Gö6976 failed to do so, thus ruling out the participation of PKC . Ang II activated nPKC´and did not affect nPKCq, pinpointing PKC´as the mediator of Ang II in p44/42 MAPK activation. Overexpression of wild-type ERK1 and ERK2 significantly reduced basal as well as Ang II-stimulated human −2023CYP11B2-CAT activity; conversely, the two dominant negative mutants increased them. Overexpression of constitutively active (ca) PKC´suppressed Ang II-induced −2023CYP11B2-CAT activity. Infection of H295R cells with adenoviruses (Adv) expressing caPKC´activated endogenous MEK1/2 and p44/42 MAPK. Adv-caPKC´inhibited Ang II-stimulated aldosterone synthase mRNA levels and this action was reversed by the MEK1 inhibitor, PD98059. Also, Ang II increased JunB protein levels and this effect was inhibited by PD98059 and Bis. Adv-caPKC´enhanced JunB protein levels and PD98059 attenuated the increase. JunB overexpression abolished the Ang II-induced promoter activity within −138 bp of the 58-flanking region of CYP11B2. Collectively, these results demonstrate that PKC inhibits CYP11B2 transcription through the p44/42 MAPK pathway and JunB in H295R cells.

show abstract

Janus Kinase 2 and Calcium Are Required for Angiotensin II-dependent Activation of Steroidogenic Acute Regulatory Protein Transcription in H295R Human Adrenocortical Cells

Cited by 36 publications

References 58 publications

Transcriptional Control of Adrenal Steroidogenesis

Transcriptional Control of Adrenal Steroidogenesis

Adipocytes, aldosterone and obesity-related hypertension

Novel protein kinase C-epsilon inhibits human CYP11B2 gene expression through ERK1/2 signalling pathway and JunB

Contact Info

Product

Resources

About