Inducible expression of protein kinase Cα suppresses steroidogenesis in Y-1 adrenocortical cells

1998 ◽  
Vol 275 (3) ◽  
pp. C780-C789 ◽  
Author(s):  
Mary E. Reyland ◽  
David L. Williams ◽  
Elizabeth K. White
Keyword(s):  
Protein Kinase ◽  
Cell Lines ◽  
Adrenocortical Cells ◽  
Chain Cleavage ◽  
Protein Kinase Cα ◽  
Cleavage Enzyme ◽  
Camp Induction ◽  
First Time ◽  
The Relationship

We have previously shown that protein kinase C (PKC) suppresses steroidogenesis in Y-1 adrenocortical cells. To ask directly if the PKCα isoform mediates this suppression, we have developed Y-1 cell lines in which PKCα is expressed from a tetracycline-regulated promoter. Induction of PKCα expression in these cell lines results in decreased P450 cholesterol side-chain cleavage enzyme (P450-SCC) activity as judged by the conversion of hydroxycholesterol to pregnenolone. Transcription of a P450-SCC promoter-luciferase construct is also reduced when PKCα expression is increased. However, expression of PKCα has no effect on 8-bromo-cAMP induction of steroidogenesis, indicating that these pathways function independently to regulate steroidogenesis. To determine the relationship between endogenous PKC activity and steroidogenesis, we examined 12 Y-1 subclones that were isolated by limited dilution cloning. In each of these subclones, steroid production correlates inversely with total PKC activity and with the expression of PKCα but not PKCε or PKCζ. These studies define for the first time the role of a specific PKC isoform (PKCα) in regulating steroidogenesis and P450-SCC activity in adrenocortical cells.

scholarly journals Resveratrol Stimulates Cortisol Biosynthesis by Activating SIRT-Dependent Deacetylation of P450scc

Endocrinology ◽  
2012 ◽  
Vol 153 (7) ◽  
pp. 3258-3268 ◽  
Author(s):  
Donghui Li ◽  
Eric B. Dammer ◽  
Marion B. Sewer
Keyword(s):  
Protein Expression ◽  
Fold Increase ◽  
Pyridine Nucleotide ◽  
Nucleotide Metabolism ◽  
Side Chain ◽  
Mitochondrial Enzyme ◽  
Adrenocortical Cells ◽  
Protein Levels ◽  
Chain Cleavage ◽  
Cleavage Enzyme

In the human adrenal cortex, cortisol is synthesized from cholesterol by members of the cytochrome P450 superfamily and hydroxysteroid dehydrogenases. Both the first and last steps of cortisol biosynthesis occur in mitochondria. Based on our previous findings that activation of ACTH signaling changes the ratio of nicotinamide adenine dinucleotide (NAD) phosphate to reduced NAD phosphate in adrenocortical cells, we hypothesized that pyridine nucleotide metabolism may regulate the activity of the mitochondrial NAD+-dependent sirtuin (SIRT) deacetylases. We show that resveratrol increases the protein expression and half-life of P450 side chain cleavage enzyme (P450scc). The effects of resveratrol on P450scc protein levels and acetylation status are dependent on SIRT3 and SIRT5 expression. Stable overexpression of SIRT3 abrogates the cellular content of acetylated P450scc, concomitant with an increase in P450scc protein expression and cortisol secretion. Mutation of K148 and K149 to alanine stabilizes the expression of P450scc and results in a 1.5-fold increase in pregnenolone biosynthesis. Finally, resveratrol also increases the protein expression of P450 11β, another mitochondrial enzyme required for cortisol biosynthesis. Collectively, this study identifies a role for NAD+-dependent SIRT deacetylase activity in regulating the expression of mitochondrial steroidogenic P450.

Role of Protein Kinase Cα in Signaling from the Histamine H1 Receptor to the Nucleus

2001 ◽  
Vol 59 (5) ◽  
pp. 1012-1021 ◽  
Author(s):  
A. C. Megson ◽  
E. M. Walker ◽  
S. J. Hill
Keyword(s):  
Protein Kinase ◽  
H1 Receptor ◽  
Histamine H1 Receptor ◽  
Protein Kinase Cα

scholarly journals MIGRATION, WAR, AND THE MAKING OF A TRANSNATIONAL LEBANESE SHIʿI COMMUNITY IN SENEGAL

2010 ◽  
Vol 42 (2) ◽  
pp. 269-290 ◽  
Author(s):  
Mara A. Leichtman
Keyword(s):  
National Identity ◽  
Public Opinion ◽  
Turning Point ◽  
West African ◽  
Local Responses ◽  
Religious Rituals ◽  
Political Ties ◽  
First Time ◽  
The Relationship

The July 2006 Lebanon war was an important turning point for West African Lebanese. For the first time since their formation as a community, the Lebanese in Senegal organized a demonstration in Dakar displaying solidarity with Lebanon. This protest illuminates the dynamics between global forces and local responses. Hizbullah's effectiveness in winning the international public opinion of both Sunni and Shiʿi Muslims in the war against Israel led to a surge in Lebanese diaspora identification, even among communities who had not been similarly affected by previous Lebanese wars. By analyzing the role of a Lebanese shaykh in bringing religious rituals and a Lebanese national identity to the community in Senegal, this article explores how members of the community maintain political ties to Lebanon even when they have never visited the “homeland” and sheds new light on the relationship among religion, migration, and (trans)nationalism.

The mediating role of maladaptive perfectionism in the association between psychological control and learned helplessness

2017 ◽  
Vol 20 (2) ◽  
pp. 113-126 ◽  
Author(s):  
Pina Filippello ◽  
Rosalba Larcan ◽  
Luana Sorrenti ◽  
Caterina Buzzai ◽  
Susanna Orecchio ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Learned Helplessness ◽  
Psychological Control ◽  
Parental Psychological Control ◽  
Mediating Role ◽  
Maladaptive Perfectionism ◽  
Relevant Role ◽  
First Time ◽  
The Relationship

Despite the extensive research on parental psychological control, no study has explored the relation between parental and teacher psychological control, maladaptive perfectionism and learned helplessness (LH). The purpose of this study was to investigate (1) whether perceived teacher psychological control predicts positively LH, (2) whether perceived parental psychological control predicts maladaptive perfectionism, and (3) whether the association between perceived parental and teacher psychological control and LH is mediated by maladaptive perfectionism. In a sample of 433 participants, 268 females (61.9%) and 165 males (38.1%), ranged in age from 13 to 19 years ( M = 15.38, standard deviation (SD) = 1.18), it was found that teacher psychological control has a more relevant role in the prediction of LH than parental control. Moreover, maladaptive perfectionism was a full mediator of the relationship between perceptions of teacher psychological control and LH. These results extend previous studies on teacher psychological control and, for the first time, provide evidence for the relation with LH, identifying maladaptive perfectionism as a variable that accounts for the relation between teacher psychological control and LH.

scholarly journals Role of the Ca2+/Phosphatidylserine Binding Region of the C2 Domain in the Translocation of Protein Kinase Cα to the Plasma Membrane

2003 ◽  
Vol 278 (12) ◽  
pp. 10282-10290 ◽  
Author(s):  
Stephen R. Bolsover ◽  
Juan C. Gomez-Fernandez ◽  
Senena Corbalan-Garcia
Keyword(s):  
Plasma Membrane ◽  
Protein Kinase ◽  
C2 Domain ◽  
Binding Region ◽  
Protein Kinase Cα

The Role of Calcium/Calmodulin-Dependent Protein Kinase Cascade on MIP-1α Gene Expression in ATL Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3877-3877
Author(s):  
Kensuke Matsumoto ◽  
Koji Murao ◽  
Hitomi Imachi ◽  
Takamasa Nishiuchi ◽  
Hiroaki Ohnishi ◽  
...  
Keyword(s):  
T Cell ◽  
Protein Kinase ◽  
Cell Lines ◽  
Transcriptional Activation ◽  
Promoter Activity ◽  
Calcium Nitrate ◽  
Dependent Manner ◽  
Dependent Protein Kinase ◽  
Dependent Protein

Abstract Adult T-cell leukemia (ATL) is a mature CD4+ T-cell malignancy caused by infection with human T-lymphotrophic virus (HTLV-1) and is associated with a marked hypercalcemia on many patients. Recently, it is proposed that Macrophage inflammatory protein-1α (MIP-1α) is the clinical hallmark of hypercalcemia in ATL, but the regulation of MIP-1α secretion has not been clarified yet. In this study, we examined the effect of calcium on the MIP-1α secretion and cell proliferation of ATL cells, and also the role of the Ca2+/calmodulin (CaM)-dependent protein kinase (CaM-K) cascade in transcriptional activation of MIP-1α. The addition of calcium nitrate to the medium enhanced the secretion of MIP-1α by ATL cell lines (ATN, MT-2, OKM-2T) and the proliferation in a dose dependent manner. The maximum response of MIP-1α secretion was induced at 10.42mM calcium in OKM-2T cells. CaM-KK selective inhibitor STO-609 inhibited the calcium dependent secretion of MIP-1α and proliferation of ATL cell lines. We investigated the effects of CaM-KK/CaM-KIV signaling pathway on MIP-1α promoter activity in OKM-2T. The transfection of CaM-KIV stimulated the MIP-1α promoter activity and the upstream kinase, CaM-KK enhanced the stimulatory effect of CaM-KIV on its activity. Furthermore, mutation of the cAMP response element (CRE) within the MIP-1α promoter significantly reduced the effect of CaM-KIV and calcium, and it wasn’t less enhanced by the addition of calcium nitrate to the medium than the wild type. Our studies have indicated that hypercalcemia enhances MIP-1α secretion and the cell growth in ATL cells, and these mechanisms require the CaM-KK/CaM-KIV cascade. These findings raise the possibility that the inhibitory of CaM-KK/CaM-KIV cascade may be of therapeutic value for ATL.

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