Bicarbonate, carbon dioxide and pH sensing via mammalian bicarbonate-regulated soluble adenylyl cyclase

Rossetti, Tom; Jackvony, Stephanie; Buck, Jochen; Levin, Lonny R.

doi:10.1098/rsfs.2020.0034

Cited by 21 publications

(22 citation statements)

References 103 publications

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“…In addition, a number of other modulators such as PKA, protein kinase C, and Ca 2+ /calmodulin protein kinase may affect tmAC activity [ 4 , 14 ]. sAC is insensitive to G proteins but can be activated by HCO 3 − [ 1 , 15 ] and the divalent metal cations, Mn 2+ and Ca 2+ [ 15 ]. Because the sAC function to synthesize cAMP is dependent on the presence of ATP, sAC senses the ATP concentration [ 16 ].…”

Section: Current Model Of Camp Signalingmentioning

confidence: 99%

Emerging Role of cAMP/AMPK Signaling

Aslam

Ladilov

2022

Cells

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The 5′-Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a natural energy sensor in mammalian cells that plays a key role in cellular and systemic energy homeostasis. At the cellular level, AMPK supports numerous processes required for energy and redox homeostasis, including mitochondrial biogenesis, autophagy, and glucose and lipid metabolism. Thus, understanding the pathways regulating AMPK activity is crucial for developing strategies to treat metabolic disorders. Mounting evidence suggests the presence of a link between cyclic AMP (cAMP) and AMPK signaling. cAMP signaling is known to be activated in circumstances of physiological and metabolic stress due to the release of stress hormones, such as adrenaline and glucagon, which is followed by activation of membrane-bound adenylyl cyclase and elevation of cellular cAMP. Because the majority of physiological stresses are associated with elevated energy consumption, it is not surprising that activation of cAMP signaling may promote AMPK activity. Aside from the physiological role of the cAMP/AMPK axis, numerous reports have suggested its role in several pathologies, including inflammation, ischemia, diabetes, obesity, and aging. Furthermore, novel reports have provided more mechanistic insight into the regulation of the cAMP/AMPK axis. In particular, the role of distinct cAMP microdomains generated by soluble adenylyl cyclase in regulating basal and induced AMPK activity has recently been demonstrated. In the present review, we discuss current advances in the understanding of the regulation of the cAMP/AMPK axis and its role in cellular homeostasis and explore some translational aspects.

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Section: Current Model Of Camp Signalingmentioning

confidence: 99%

Emerging Role of cAMP/AMPK Signaling

Aslam

Ladilov

2022

Cells

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“…These receptors belong to different types of proteins, in which the most well-studied are as follows: (1) ion channels, such as acidsensing ion channels (ASIC) [8], the renal outer medullary K + channel (ROMK) [101], TWIK-related acid-sensitive K + channel (TASK) [6], and transient receptor potential channels (TRP) [87]; (2) tyrosine kinases, such as insulin receptor-related receptor (IRRR) [14]; and (3) G protein-coupled receptors (GPCRs), the topic of this review. There are also additional types of acid-base sensing molecules, such as the bicarbonate/CO 2 -sensing protein receptor protein tyrosine phosphatase (RPTPgamma) [4], the soluble adenylyl cyclase (sAC) [106], or the pH-sensitive Pyk2 kinase [69].…”

Section: Introductionmentioning

confidence: 99%

Physiological relevance of proton-activated GPCRs

Silva

Wagner

2022

Pflugers Arch - Eur J Physiol

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The detection of H+ concentration variations in the extracellular milieu is accomplished by a series of specialized and non-specialized pH-sensing mechanisms. The proton-activated G protein–coupled receptors (GPCRs) GPR4 (Gpr4), TDAG8 (Gpr65), and OGR1 (Gpr68) form a subfamily of proteins capable of triggering intracellular signaling in response to alterations in extracellular pH around physiological values, i.e., in the range between pH 7.5 and 6.5. Expression of these receptors is widespread for GPR4 and OGR1 with particularly high levels in endothelial cells and vascular smooth muscle cells, respectively, while expression of TDAG8 appears to be more restricted to the immune compartment. These receptors have been linked to several well-studied pH-dependent physiological activities including central control of respiration, renal adaption to changes in acid–base status, secretion of insulin and peripheral responsiveness to insulin, mechanosensation, and cellular chemotaxis. Their role in pathological processes such as the genesis and progression of several inflammatory diseases (asthma, inflammatory bowel disease), and tumor cell metabolism and invasiveness, is increasingly receiving more attention and makes these receptors novel and interesting targets for therapy. In this review, we cover the role of these receptors in physiological processes and will briefly discuss some implications for disease processes.

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“…Following that, the authors provide information on the role of CO 2 in mitochondrial function and the demonstration that CO 2 protects against oxidative stress. The review expands to describe the influence of CO 2 on the regulation of intracellular calcium as well as how CO 2 interacts with the cyclic adenosine monophosphate (cAMP) and AMP-activated ser/thr protein kinases pathways; further work on the relationship between cAMP and CO 2 is also expanded on in a later review [4] and research article [5]. The review then summarizes the various responses to CO 2 by transcription factors, including a discussion of hypercapnia and the NF-κB pathway, which links CO 2 to immunity and inflammation (further presented in theme 4).…”

Section: Theme 2—carbon Dioxide In the Animal Kingdommentioning

confidence: 99%

“…cAMP has roles in biological processes ranging from development through to apoptosis and provides a direct link between [HCnormalO3−] and the adaptive response. Rosetti et al have reviewed the relationship between sAC and the physiological HCnormalO3−/CO 2 /pH environment [4]. The review outlines the ways through which sAC functions as both HCnormalO3− sensor and CO 2 /pH sensor due to the high abundance of carbonic anhydrase catalysing the equilibration of CO 2 , HCnormalO3− and protons within the extracellular and intracellular environments.…”

Section: Theme 2—carbon Dioxide In the Animal Kingdommentioning

confidence: 99%