Variation of chemosensory receptor content of Campylobacter jejuni strains and modulation of receptor gene expression under different in vivo and in vitro growth conditions

Bradykinin has vasodilatory and tissue-protective effects exerted via its B2 type receptor, whereas the B1 receptor is constitutively absent but inducible by inflammation and toxins. In previous studies, we found that B2 receptor gene knockout mice exhibit overexpression of the B1 receptor, which assumes a vasodilatory function and is further upgraded in renovascular hypertension. The present study was designed to explore the effects of excess angiotensin II (ANG II) on B1 receptor and B2 receptor gene expression in mouse cardiomyocytes and rat vascular smooth muscle cells (VSMC) in vivo (after a 3-day infusion of 30 ng/min ANG II in 11 wild-type and in 13 genetically engineered mice with deleted B2 receptor gene) and in vitro (ANG II added in rat VSMC culture in the presence or absence of AT1 or AT2 receptor antagonist). Expression of B1 and B2 receptor mRNA was assessed by reverse transcriptase-polymerase chain reaction. ANG II infusion caused upregulation by 30% of the already significantly overexpressed B1 receptors in cardiomyocytes of the B2receptor gene knockout mice, but in the wild-type mice it upregulated only the B2 receptor mRNA by 47%. The addition of ANG II in VSMC culture produced a time-dependent induction of B1and upregulation of B2 receptor gene expression, maximal at 3 h (by fivefold), declining almost to baseline by 24 h. The addition of losartan completely blocked this effect, whereas the AT2 blocker PD-123319 made no difference, indicating that this is an AT1-mediated effect of ANG II. The data indicate that excess ANG II in subpressor doses in vivo upregulates expression of the B2 receptor, but in its absence, the already overexpressed B1 receptor is further upregulated, evidently assuming a counterregulatory response; in vitro, it transiently upregulates both bradykinin receptors.

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Effects of BDNF, T3, and corticosterone on expression of the hypothalamic obesity gene network in vivo and in vitro

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.90813.2008 ◽

2009 ◽

Vol 296 (4) ◽

pp. R1180-R1189 ◽

Cited By ~ 30

Author(s):

Mardi S. Byerly ◽

Jean Simon ◽

Elisabeth Lebihan-Duval ◽

Michel J. Duclos ◽

Larry A. Cogburn ◽

...

Keyword(s):

Gene Expression ◽

Body Composition ◽

Leptin Receptor ◽

Receptor Gene ◽

Energy Regulation ◽

Underlying Mechanisms ◽

Agouti Related Protein ◽

Receptor Gene Expression

Hypothalamic neuropeptides, neurotrophins, and systemic hormones modulate food intake and body composition. Although advances toward elucidating these interactions have been made, many aspects of the underlying mechanisms remain vague. Hypothalami from fat and lean chicken lines were assessed for differential expression of anabolic/orexigenic and catabolic/anorexigenic genes. Effects of triiodothyronine (T3), corticosterone (Cort), and brain-derived neurotrophic factor (BDNF) on expression of anabolic/orexigenic and catabolic/anorexigenic genes were tested in cultures of hypothalamic neurons. From this, we found that BDNF increased and T3 decreased gene expression for BDNF, leptin receptor (LEPR), pro-opiomelanocortin (POMC), thyrotropin releasing hormone (TRH), and agouti-related protein (AGRP). Thyroid hormone levels were manipulated during development to show that T3 inhibited BDNF, TRH, and BDNF receptor gene expression. Delivery of T3, Cort, T3 plus Cort, or vehicle in vivo continuously for 72 h indicated that Cort and T3 have overlapping roles in regulating TRH, LEPR, and POMC gene expression and that Cort and T3 regulate BDNF, neuropeptide Y, and AGRP in opposite directions. Collectively, these findings suggest that interactions between the neuropeptide BDNF and the hormones T3 and/or Cort may constitute a homeostatic mechanism that links hypothalamic energy regulation controlling body composition.

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c-Jun N-Terminal Kinase Activation of Activator Protein-1 Underlies Homologous Regulation of the Gonadotropin-Releasing Hormone Receptor Gene in αT3-1 Cells

Endocrinology ◽

10.1210/en.2002-220784 ◽

2003 ◽

Vol 144 (3) ◽

pp. 839-849 ◽

Cited By ~ 24

Author(s):

Buffy S. Ellsworth ◽

Brett R. White ◽

Ann T. Burns ◽

Brian D. Cherrington ◽

Annette M. Otis ◽

...

Keyword(s):

Gene Expression ◽

Protein Kinase ◽

Cell Model ◽

Receptor Gene ◽

Critical Role ◽

Dominant Negative ◽

Activator Protein 1 ◽

Activator Protein

Reproductive function is dependent on the interaction between GnRH and its cognate receptor found on gonadotrope cells of the anterior pituitary gland. GnRH activation of the GnRH receptor (GnRHR) is a potent stimulus for increased expression of multiple genes including the gene encoding the GnRHR itself. Thus, homologous regulation of the GnRHR is an important mechanism underlying gonadotrope sensitivity to GnRH. Previously, we have found that GnRH induction of GnRHR gene expression in αT3-1 cells is partially mediated by protein kinase C activation of a canonical activator protein-1 (AP-1) element. In contrast, protein kinase A and a cAMP response element-like element have been implicated in mediating the GnRH response of the GnRHR gene using a heterologous cell model (GGH3). Herein we find that selective removal of the canonical AP-1 site leads to a loss of GnRH regulation of the GnRHR promoter in transgenic mice. Thus, an intact AP-1 element is necessary for GnRH responsiveness of the GnRHR gene both in vitro and in vivo. Based on in vitro analyses, GnRH appeared to enhance the interaction of JunD, FosB, and c-Fos at the GnRHR AP-1 element. Although enhanced binding of cFos reflected an increase in gene expression, GnRH appeared to regulate both FosB and JunD at a posttranslational level. Neither overexpression of a constitutively active Raf-kinase nor pharmacological blockade of GnRH-induced ERK activation eliminated the GnRH response of the GnRHR promoter. GnRH responsiveness was, however, lost in αT3-1 cells that stably express a dominant-negative c-Jun N-terminal kinase (JNK) kinase, suggesting a critical role for JNK in mediating GnRH regulation of the GnRHR gene. Consistent with this possibility, we find that the ability of forskolin and membrane-permeable forms of cAMP to inhibit the GnRH response of the GnRHR promoter is associated with a loss of both JNK activation and GnRH-mediated recruitment of the primary AP-1-binding components.

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