Adenylyl cyclase type 5 in cardiac disease, metabolism, and aging

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Adenylyl cyclase type 5 in cardiac disease, metabolism, and aging.

G protein-coupled receptor/adenylyl cyclase (AC)/cAMP signaling is crucial for all cellular responses to physiological and pathophysiological stimuli. There are nine isoforms of membrane-bound AC, with type 5 being one of the two major isoforms in the heart. Since the role of AC in the heart in regulating cAMP and acute changes in inotropic and chronotropic state are well known, this review wil...

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Inhibition of Adenylyl Cyclase Type 5 Increases Longevity and Healthful Aging through Oxidative Stress Protection

Mice with disruption of adenylyl cyclase type 5 (AC5 knockout, KO) live a third longer than littermates. The mechanism, in part, involves the MEK/ERK pathway, which in turn is related to protection against oxidative stress. The AC5 KO model also protects against diabetes, obesity, and the cardiomyopathy induced by aging, diabetes, and cardiac stress and also demonstrates improved exercise capac...

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Adenylyl cyclase type 5 protein expression during cardiac development and stress.

Adenylyl cyclase (AC) types 5 and 6 (AC5 and AC6) are the two major AC isoforms expressed in the mammalian heart that mediate signals from beta-adrenergic receptor stimulation. Because of the unavailability of isoform-specific antibodies, it is difficult to ascertain the expression levels of AC5 protein in the heart. Here we demonstrated the successful generation of an AC5 isoform-specific mous...

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N terminus of type 5 adenylyl cyclase scaffolds Gs heterotrimer.

According to accepted doctrine, agonist-bound G protein-coupled receptors catalyze the exchange of GDP for GTP and facilitate the dissociation of Galpha and Gbetagamma, which in turn regulate their respective effectors. More recently, the existence of preformed signaling complexes, which may include receptors, heterotrimeric G proteins, and/or effectors, is gaining acceptance. We show herein th...

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Type 5 adenylyl cyclase disruption leads to enhanced exercise performance

The most important physiological mechanism mediating enhanced exercise performance is increased sympathetic, beta adrenergic receptor (β-AR), and adenylyl cyclase (AC) activity. This is the first report of decreased AC activity mediating increased exercise performance. We demonstrated that AC5 disruption, that is, knock out (KO) mice, a longevity model, increases exercise performance. Important...

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ژورنال

عنوان ژورنال: American Journal of Physiology-Heart and Circulatory Physiology

سال: 2013

ISSN: 0363-6135,1522-1539

DOI: 10.1152/ajpheart.00080.2013