Abstract 220: Transcriptional Analysis Of Caveolin And Cavin In The Male And Female Ageing Mouse Heart Following Ischemic Stress

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Can J Kiessling ◽  
Melissa Reichelt ◽  
John Headrick ◽  
Kevin Ashton
Keyword(s):  
G Protein ◽  
Ischemic Tolerance ◽  
Transcriptional Analysis ◽  
Membrane Microdomains ◽  
G Protein Coupled Receptor ◽  
Male And Female ◽  
Female Mice ◽  
Age Related ◽  
G Protein Coupled ◽  
Ischemic Stress

Cardioprotection against infarction and dysfunction in the myocardium involves G-protein-coupled receptor signalling orchestrated by specialised membrane microdomains termed caveolae. The caveolin protein family consist of three subtypes: caveolin-1, −2 and −3 (Cav1-3) and are responsible for the formation of caveolae and hypothesized to orchestrate cardioprotective signalling. Caveolin-3 deficiency and overexpression has been shown to attenuate and restore cardioprotection, respectively. Recently, a family of four related proteins known as cavins (Cavin1-4) have been implicated as regulators of caveolae formation and function. The roles and expression distribution of the cavin family is currently unknown in cardiac tissue. In this study hearts were isolated from 8, 16, 32 and 48 week male and female mice and subjected to normoxic perfusion (80 min) or ischemic stress (20 min global ischemia, 60 min reperfusion). RT-qPCR was used to assess differential gene expression of caveolin and cavin subtypes across these ages in both sexes. Decreased post-ischemic pressure development and increased LDH release were observed in 32 and 48 week old relative to 8 week old male hearts hearts, indicative of age-related loss of ischemic tolerance. Females showed greater tolerance to ischemia at 32 and 48 week old hearts when compared to male counterparts. In normoxic male 48 week old hearts, Cav1,-2,-3 and Cavin1 were significantly repressed, whilst post-ischemic male 48 week old hearts demonstrated significant repression of Cav3 and Cavin1 only. Normoxic female hearts showed no significant changes in caveolin and cavin transcript expression over the aging time course. However, post-ischemic female 48 week old hearts showing significant down-regulation of Cav3 only. Taken together, alterations in caveolin and cavin expression may contribute to the age-related loss of ischemic tolerance and G-protein-coupled receptor-mediated protection in aging male and female mice hearts.

Activation of the G-protein coupled receptor 30 (GPR30) has different effects on anxiety in male and female mice

Steroids ◽  
2014 ◽  
Vol 81 ◽  
pp. 49-56 ◽  
Author(s):  
David Hart ◽  
Mary Nilges ◽  
Kevin Pollard ◽  
Tucker Lynn ◽  
Olivia Patsos ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptor ◽  
Male And Female ◽  
Female Mice ◽  
G Protein Coupled

scholarly journals Sex Differences in High Fat Diet-Induced Metabolic Alterations Correlate with Changes in the Modulation of GRK2 Levels

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1464 ◽  
Author(s):  
Alba C. Arcones ◽  
Marta Cruces-Sande ◽  
Paula Ramos ◽  
Federico Mayor ◽  
Cristina Murga
Keyword(s):  
Insulin Resistance ◽  
G Protein ◽  
High Fat Diet ◽  
High Fat ◽  
G Protein Coupled Receptor ◽  
Metabolic Alterations ◽  
Female Mice ◽  
Protein Levels ◽  
Age Related ◽  
G Protein Coupled

A differential sex-related sensitivity has been reported in obesity and insulin resistance-related cardio-metabolic diseases, with a lower incidence of these pathologies being observed in young females when compared to age-matched males. However, such relative protection is lost with age. The mechanisms underlying such sex and age-related changes in the susceptibility to diabetes and obesity are not fully understood. Herein, we report that the relative protection that is displayed by young female mice, as compared to male littermates, against some of the metabolic alterations that are induced by feeding a high fat diet (HFD), correlates with a lower upregulation of the protein levels of G protein-coupled receptor kinase (GRK2), which is a key regulator of both insulin and G protein-coupled receptor signaling, in the liver and adipose tissue. Interestingly, when the HFD is initiated in middle-aged (32 weeks) female mice, these animals are no longer protected and display a more overt obese and insulin-resistant phenotype, along with a more evident increase in the GRK2 protein levels in metabolically relevant tissues in such conditions. Our data suggest that GRK2 dosage might be involved in the sex and age-biased sensitivity to insulin resistance-related pathologies.

scholarly journals Activation of Estrogen Receptor G Protein–Coupled Receptor 30 Enhances Cholesterol Cholelithogenesis in Female Mice

Hepatology ◽  
2020 ◽  
Vol 72 (6) ◽  
pp. 2077-2089 ◽  
Author(s):  
Helen H. Wang ◽  
Ornella Bari ◽  
Christopher K. Arnatt ◽  
Min Liu ◽  
Piero Portincasa ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
G Protein ◽  
G Protein Coupled Receptor ◽  
Female Mice ◽  
G Protein Coupled

Impact of Aging and G Protein‐Coupled Estrogen Receptor Deletion in Arterial Stiffening and Cardiac Function in Male and Female Mice

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Benard Ojwang Ogola ◽  
Margaret A. Zimmerman ◽  
Nicholas R. Harris ◽  
Isabella Kilanowski-Doroh ◽  
Leanne Groban ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Cardiac Function ◽  
G Protein ◽  
Male And Female ◽  
Arterial Stiffening ◽  
Female Mice ◽  
G Protein Coupled

scholarly journals Deletion of the G Protein-Coupled Receptor 30 Impairs Glucose Tolerance, Reduces Bone Growth, Increases Blood Pressure, and Eliminates Estradiol-Stimulated Insulin Release in Female Mice

Endocrinology ◽  
2009 ◽  
Vol 150 (2) ◽  
pp. 687-698 ◽  
Author(s):  
Ulrika E. A. Mårtensson ◽  
S. Albert Salehi ◽  
Sara Windahl ◽  
Maria F. Gomez ◽  
Karl Swärd ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Glucose Tolerance ◽  
G Protein ◽  
Insulin Release ◽  
Bone Growth ◽  
G Protein Coupled Receptor ◽  
Female Mice ◽  
G Protein Coupled

In vitro studies suggest that the G protein-coupled receptor (GPR) 30 is a functional estrogen receptor. However, the physiological role of GPR30 in vivo is unknown, and it remains to be determined whether GPR30 is an estrogen receptor also in vivo. To this end, we studied the effects of disrupting the GPR30 gene in female and male mice. Female GPR30(−/−) mice had hyperglycemia and impaired glucose tolerance, reduced body growth, increased blood pressure, and reduced serum IGF-I levels. The reduced growth correlated with a proportional decrease in skeletal development. The elevated blood pressure was associated with an increased vascular resistance manifested as an increased media to lumen ratio of the resistance arteries. The hyperglycemia and impaired glucose tolerance in vivo were associated with decreased insulin expression and release in vivo and in vitro in isolated pancreatic islets. GPR30 is expressed in islets, and GPR30 deletion abolished estradiol-stimulated insulin release both in vivo in ovariectomized adult mice and in vitro in isolated islets. Our findings show that GPR30 is important for several metabolic functions in female mice, including estradiol-stimulated insulin release. The G protein-coupled receptor GPR30 maintains normal bone growth, glucose homeostasis, and blood pressure, and mediates estradiol-stimulated insulin release in female mice.

Endothelium-dependent relaxation by G protein-coupled receptor 30 agonists in rat carotid arteries

2010 ◽  
Vol 298 (3) ◽  
pp. H1055-H1061 ◽  
Author(s):  
Brad R. S. Broughton ◽  
Alyson A. Miller ◽  
Christopher G. Sobey
Keyword(s):  
Nitric Oxide ◽  
G Protein ◽  
Arterial Wall ◽  
Carotid Arteries ◽  
Female Rats ◽  
Sprague Dawley ◽  
G Protein Coupled Receptor ◽  
Male And Female ◽  
Male And Female Rats ◽  
G Protein Coupled

Recent studies have identified that the novel membrane estrogen receptor, G protein-coupled receptor 30 (GPR30), is present in blood vessels. However, the signaling mechanisms associated with GPR30 in the vasculature remain unclear. We examined whether putative agonists of GPR30 exert vasorelaxant and/or antioxidant effects similar to those reported for estrogen. Using wire myography, we assessed the role of the endothelium in relaxation responses to the GPR30 agonists, G-1 and 5408-0877 (1 nM-10 μM), in U-46619-precontracted common carotid arteries from Sprague-Dawley rats. Furthermore, using lucigenin (5 μM)-enhanced chemiluminescence, we tested the effect of G-1 (10 μM) on superoxide levels. Specific immunofluorescence was also used to confirm GPR30 expression in the arterial wall. We found that G-1 and 5408-0877 induced a concentration-dependent relaxation in carotid arteries from both male and female rats. Interestingly, G-1- and 5408-0877-induced relaxation was abolished by endothelium removal and abrogated in the presence of the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (100 μM). In addition, G-1 significantly decreased NADPH (100 μM)-stimulated superoxide production by carotid and intracranial (pooled basilar and middle cerebral) arteries but also attenuated the superoxide signal detected in a cell-free xanthine/xanthine oxidase assay. Furthermore, GPR30 immunoreactivity was observed in endothelial and vascular smooth muscle cells of carotid arteries from both genders. These findings indicate that GPR30 is expressed throughout the arterial wall and that GPR30 agonists elicit endothelial-derived nitric oxide-dependent relaxation of the carotid artery in male and female rats. Additionally, G-1 appears to directly scavenge superoxide anion.

scholarly journals A G-Protein Coupled Receptor and Macular Degeneration

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 910
Author(s):  
Anna G. Figueroa ◽  
Brian S. McKay
Keyword(s):  
Macular Degeneration ◽  
G Protein ◽  
Racial Bias ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
G Protein Coupled Receptor ◽  
Primary Defect ◽  
Age Related ◽  
G Protein Coupled

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the world. The risk of AMD increases with age and is most common among the white population. Here, we discuss the convergence of factors related to race, pigmentation, and susceptibility to AMD, where the primary defect occurs in retinal support cells, the retinal pigment epithelium (RPE). We explore whether the observed racial bias in AMD incidence is related to innate differences in the basal level of pigmentation between races, and whether the pigmentation pathway activity in the RPE might protect from retinal degeneration. More specifically, we explore whether the downstream signaling activity of GPR143, a G-protein coupled receptor in the pigmentation pathway, might underly the racial bias of AMD and be a target to prevent the disease. Lastly, we summarize the past findings of a large retrospective study that investigated the relationship between the stimulation of GPR143 with L-DOPA, the pigmentation pathway, and AMD, to potentially help develop new ways to prevent or treat AMD. The reader of this review will come to understand the racial bias of AMD, which is related to the function of the RPE.

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