The local corticotropin-releasing hormone receptor 2 signalling pathway partly mediates hypoxia-induced increases in lipolysis via the cAMP–protein kinase A signalling pathway in white adipose tissue

Abstract Mice lacking the RIIβ regulatory subunit of protein kinase A exhibit a 50% reduction in white adipose tissue stores compared with wild-type littermates and are resistant to diet-induced obesity. RIIβ−/− mice also have an increase in resting oxygen consumption along with a 4-fold increase in the brown adipose-specific mitochondrial uncoupling protein 1 (UCP1). In this study, we examined the basis for UCP1 induction and tested the hypothesis that the induced levels of UCP1 in RIIβ null mice are essential for the lean phenotype. The induction of UCP1 occurred at the protein but not the mRNA level and correlated with an increase in mitochondria in brown adipose tissue. Mice lacking both RIIβ and UCP1 (RIIβ−/−/Ucp1−/−) were created, and the key parameters of metabolism and body composition were studied. We discovered that RIIβ−/− mice exhibit nocturnal hyperactivity in addition to the increased oxygen consumption at rest. Disruption of UCP1 in RIIβ−/− mice reduced basal oxygen consumption but did not prevent the nocturnal hyperactivity. The double knockout animals also retained the lean phenotype of the RIIβ null mice, demonstrating that induction of UCP1 and increased resting oxygen consumption is not the cause of leanness in the RIIβ mutant mice.

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Thyroid hormone-induced morphological differentiation and maturation of astrocytes involves activation of protein kinase A and ERK signalling pathway

European Journal of Neuroscience ◽

10.1111/j.1460-9568.2005.04351.x ◽

2005 ◽

Vol 22 (7) ◽

pp. 1609-1617 ◽

Cited By ~ 27

Author(s):

Mausam Ghosh ◽

Kusumika Gharami ◽

Surojit Paul ◽

Sumantra Das

Keyword(s):

Thyroid Hormone ◽

Protein Kinase ◽

Protein Kinase A ◽

Morphological Differentiation ◽

Signalling Pathway ◽

Kinase A

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cAMP-positive regulation of angiotensinogen gene expression and protein secretion in rat adipose tissue

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00188.2003 ◽

2004 ◽

Vol 286 (3) ◽

pp. E434-E438 ◽

Cited By ~ 9

Author(s):

Valérie Serazin ◽

Marie-Noelle Dieudonné ◽

Mireille Morot ◽

Philippe de Mazancourt ◽

Yves Giudicelli

Keyword(s):

Adipose Tissue ◽

Protein Kinase ◽

Protein Kinase A ◽

Protein Secretion ◽

Intracellular Camp ◽

Pathological State ◽

Mrna Levels ◽

Adrenergic Stimulation ◽

Rat Adipose Tissue ◽

Kinase A

The adipose renin-angiotensin system (RAS) has been assigned to participate in the control of adipose tissue development and in the pathogenesis of obesity-related hypertension. In adipose cells, the biological responses to β-adrenergic stimulation are mediated by an increase in intracellular cAMP. Because cAMP is known to promote adipogenesis and because an association exists between body fat mass, hypertension, and increased sympathetic stimulation, we examined the influence of cAMP on angiotensinogen (ATG) expression and secretion in rat adipose tissue. Exposure of primary cultured differentiated preadipocytes to the cAMP analog 8-bromoadenosine 3′,5′-cyclic monophosphate (8-BrcAMP) or cAMP-stimulating agents (forskolin and IBMX) results in a significant increase in ATG mRNA levels. In adipose tissue fragments, 8-BrcAMP also increases ATG mRNA levels and protein secretion, but not in the presence of the protein kinase A inhibitor H89. The addition of isoproterenol, known to stimulate the synthesis of intracellular cAMP via β-adrenoreceptors, had the same stimulatory effect on ATG expression and secretion. These results indicate that cAMP in vitro upregulates ATG expression and secretion in rat adipose tissue via the protein kinase A-dependent pathway. Further studies are required to determine whether this regulatory pathway is activated in human obesity, where increased sympathetic tone is frequently observed, and to elucidate the importance of adipose ATG to the elevated blood pressure observed in this pathological state.

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The control of blood platelets by cAMP signalling

Biochemical Society Transactions ◽

10.1042/bst20130278 ◽

2014 ◽

Vol 42 (2) ◽

pp. 289-294 ◽

Cited By ~ 13

Author(s):

Zaher Raslan ◽

Khalid M. Naseem

Keyword(s):

Protein Kinase ◽

Protein Kinase A ◽

Platelet Activation ◽

Blood Platelets ◽

Blood Platelet ◽

Platelet Inhibition ◽

Signalling Pathway ◽

Current Understanding ◽

Camp Signalling ◽

Kinase A

Blood platelet activation must be tightly regulated to ensure a balance between haemostasis and thrombosis. The cAMP signalling pathway is the most powerful endogenous regulator of blood platelet activation. PKA (protein kinase A), the foremost effector of cAMP signalling in platelets, phosphorylates a number of proteins that are thought to modulate multiple aspects of platelet activation. In the present mini-review, we outline our current understanding of cAMP-mediated platelet inhibition and discuss some of the issues that require clarification.

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