Functional implications of limited leptin receptor and ghrelin receptor coexpression in the brain.

The hormones leptin and ghrelin act in apposition to one another in the regulation of body weight homeostasis. Interestingly, both leptin receptor expression and ghrelin receptor expression have been observed within many of the same nuclei of the central nervous system (CNS), suggesting that these hormones may act on a common population of neurons to produce changes in food intake and energy expenditure. In the present study we explored the extent of this putative direct leptin and ghrelin interaction in the CNS and addressed the question of whether a loss of ghrelin signaling would affect sensitivity to leptin.

Ghrelin increases the rewarding value of high-fat diet in an orexin-dependent manner.

Background: Ghrelin is a potent orexigenic hormone that likely impacts eating via several mechanisms. Here, we hypothesized that ghrelin can regulate extra homeostatic, hedonic aspects of eating behavior.

Methods: In the current study, we assessed the effects of different pharmacological, physiological, and genetic models of increased ghrelin and/or ghrelin-signaling blockade on two classic behavioral tests of reward behavior: conditioned place preference (CPP) and operant conditioning.

Colocalization of ghrelin O-acyltransferase and ghrelin in gastric mucosal cells.

Ghrelin is a peptide hormone with many known functions, including orexigenic, blood glucose-regulatory, and antidepressant actions, among others. Mature ghrelin is unique in that it is the only known naturally occurring peptide to be posttranslationally modified by O-acylation with octanoate. This acylation is required for many of ghrelin's actions, including its effects on promoting increases in food intake and body weight.

Characterization of a novel ghrelin cell reporter mouse.

Ghrelin is a hormone that influences many physiological processes and behaviors, such as food intake, insulin and growth hormone release, and a coordinated response to chronic stress. However, little is known about the molecular pathways governing ghrelin release and ghrelin cell function. To better study ghrelin cell physiology, we have generated several transgenic mouse lines expressing humanized Renilla reniformis green fluorescent protein (hrGFP) under the control of the mouse ghrelin promoter.

Aggressive melanoma cells escape from BMP7-mediated autocrine growth inhibition through coordinated Noggin upregulation.

Bone morphogenetic proteins (BMPs) are members of the TGF-beta superfamily responsible for mediating a diverse array of cellular functions both during embryogenesis and in adult life. Previously, we reported that upregulation of BMP7 in human melanoma correlates with tumor progression. However, melanoma cells are either inhibited by or become resistant to BMP7 as a function of tumor progression, with normal melanocytes being most susceptible.

The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress.

We found that increasing ghrelin levels, through subcutaneous injections or calorie restriction, produced anxiolytic- and antidepressant-like responses in the elevated plus maze and forced swim test. Moreover, chronic social defeat stress, a rodent model of depression, persistently increased ghrelin levels, whereas growth hormone secretagogue receptor (Ghsr) null mice showed increased deleterious effects of chronic defeat. Together, these findings demonstrate a previously unknown function for ghrelin in defending against depressive-like symptoms of chronic stress.

TFIIA plays a role in the response to oxidative stress.

To characterize the role of the general transcription factor TFIIA in the regulation of gene expression by RNA polymerase II, we examined the transcriptional profiles of TFIIA mutants of Saccharomyces cerevisiae using DNA microarrays. Whole-genome expression profiles were determined for three different mutants with mutations in the gene coding for the small subunit of TFIIA, TOA2. Depending on the particular mutant strain, approximately 11 to 27% of the expressed genes exhibit altered message levels.

Oxidant-specific folding of Yap1p regulates both transcriptional activation and nuclear localization.

The yeast transcriptional regulator Yap1p is a key determinant in oxidative stress resistance. This protein is found in the cytoplasm under non-stressed conditions but rapidly accumulates in the nucleus following oxidant exposure. There it activates transcription of genes encoding antioxidants that return the redox balance of the cell to an acceptable range.

Bone morphogenetic proteins in melanoma: angel or devil?

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta (TGF-beta) superfamily serving multiple functions in many cell and tissue types including proliferation, apoptosis, differentiation, chemotaxis, angiogenesis, and matrix production during embryogenic development as well as in adult life. Despite the tremendous progress in delineating functional derangements of BMP pathways in carcinogenesis during the last decade, the biological significance of BMPs in human melanoma has received very little attention. It is now clear that biological responses to BMPs are cell type-specific and divergent effects, i.

YBP1 and its homologue YBP2/YBH1 influence oxidative-stress tolerance by nonidentical mechanisms in Saccharomyces cerevisiae.

In the yeast Saccharomyces cerevisiae, the transcription factor Yap1p is a central determinant of resistance to oxidative stress. Previous work has demonstrated that Yap1p is recruited from the cytoplasm to the nucleus upon exposure to the oxidants diamide and H2O2 in a process that requires the transient covalent linkage of the glutathione peroxidase Gpx3p to Yap1p. Genetic and biochemical analyses indicate that while both oxidants trigger nuclear accumulation of Yap1p, the function and regulation of this transcription factor is different under these two different oxidative stresses.