Protective role of soluble adenylyl cyclase against reperfusion-induced injury of cardiac cells

Rinaldi, Laura; Pozdniakova, Sofya; Jayarajan, Vignesh; Troidl, Christian; Abdallah, Yaser; Aslam, Muhammad; Ladilov, Yury

doi:10.1016/j.bbadis.2018.07.021

Cited by 12 publications

(14 citation statements)

References 29 publications

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“…To prove whether the beneficial effect of PDE2 inhibition may be translated to cardiac pathology, adult rat cardiomyocytes were challenged metabolically with cyanide followed by a recovery phase. Inhibition of PDE2A with BAY60-7550 significantly improved cell viability [ 122 ]. In alignment with these results, a recent report suggested that PDE2 inhibition has a protective effect in a brain ischemia/reperfusion model, although it was delayed rather than acute effects of reperfusion that were analyzed [ 123 ].…”

Section: Functional Role Of Sac In Different Cellular Compartmentsmentioning

confidence: 99%

Functional Significance of the Adcy10-Dependent Intracellular cAMP Compartments

Pozdniakova

Ladilov

2018

JCDD

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Mounting evidence confirms the compartmentalized structure of evolutionarily conserved 3′–5′-cyclic adenosine monophosphate (cAMP) signaling, which allows for simultaneous participation in a wide variety of physiological functions and ensures specificity, selectivity and signal strength. One important player in cAMP signaling is soluble adenylyl cyclase (sAC). The intracellular localization of sAC allows for the formation of unique intracellular cAMP microdomains that control various physiological and pathological processes. This review is focused on the functional role of sAC-produced cAMP. In particular, we examine the role of sAC-cAMP in different cellular compartments, such as cytosol, nucleus and mitochondria.

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Section: Functional Role Of Sac In Different Cellular Compartmentsmentioning

confidence: 99%

Functional Significance of the Adcy10-Dependent Intracellular cAMP Compartments

Pozdniakova

Ladilov

2018

JCDD

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“…The group initially demonst rated that diminished mitochondrial cAMP content is detrimental and exacerbates reperfusion damage post ischemia. On the other hand, overexpression of sAC improves cardiac cell viability [160]. Elevated mitochondrial cAMP content subsequently promotes PKA-dependent phosphorylation and activation of cytochrome c oxidase, enhancing ATP synthesis and attenuates ROS production as reported elsewhere [160,161].…”

Section: Myocardial Infarction (Mi) / Reperfusion Injurymentioning

confidence: 81%

“…On the other hand, overexpression of sAC improves cardiac cell viability [160]. Elevated mitochondrial cAMP content subsequently promotes PKA-dependent phosphorylation and activation of cytochrome c oxidase, enhancing ATP synthesis and attenuates ROS production as reported elsewhere [160,161]. PDE2 inhibition during reperfusion and ischemia resulted in a specific increase in mitochondrial cAMP content, improved cell survival and accelerated recovery of cytosolic Ca 2+ homeostasis [160].…”

Section: Myocardial Infarction (Mi) / Reperfusion Injurymentioning

confidence: 84%

Therapeutic Implications for PDE2 and cGMP/cAMP Mediated Crosstalk in Cardiovascular Diseases

Sadek¹,

Cachorro²,

Kämmerer³

et al. 2020

Preprint

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Phosphodiesterases (PDEs) are the principal superfamily of enzymes responsible for degrading the secondary messengers 3’,5’-cyclic nucleotides cAMP and cGMP. Their refined subcellular localization and substrate specificity contribute to finely regulate cAMP/cGMP gradients in various cellular microdomains. Redistribution of multiple signal compartmentalization components is often perceived under pathological conditions. Thereby PDEs have long been pursued as therapeutic targets in diverse disease conditions including neurological, metabolic, cancer and autoimmune disorders in addition to numerous cardiovascular diseases. PDE2 is a unique member of the broad family of PDEs. In addition to its capability to hydrolyze both cAMP and cGMP, PDE2 is the sole isoform that may be allosterically activated by cGMP increasing its cAMP hydrolyzing activity. Within the cardiovascular system, PDE2 serves as an integral regulator for the crosstalk between cAMP/cGMP pathways and thereby may couple chronically adverse augmented cAMP signalling with cardioprotective cGMP signalling. This review provides a comprehensive overview of PDE2 regulatory functions in multiple cellular components within the cardiovascular system and also within various subcellular microdomains. Implications for PDE2 mediated crosstalk mechanisms in diverse cardiovascular pathologies are discussed highlighting the prospective use of PDE2 as a potential therapeutic target in cardiovascular disorders.

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“…The group initially demonstrated that diminished mitochondrial cAMP content is detrimental and exacerbates reperfusion damage post ischemia. On the other hand, overexpression of sAC improves cardiac cell viability [ 184 ]. Elevated mitochondrial cAMP content subsequently promotes PKA-dependent phosphorylation and activation of cytochrome c oxidase, enhancing ATP synthesis and attenuates ROS production as reported previously [ 184 , 185 ].…”

Section: Role Of Pde2 In Cardiovascular Diseasementioning

confidence: 99%

“…On the other hand, overexpression of sAC improves cardiac cell viability [ 184 ]. Elevated mitochondrial cAMP content subsequently promotes PKA-dependent phosphorylation and activation of cytochrome c oxidase, enhancing ATP synthesis and attenuates ROS production as reported previously [ 184 , 185 ]. PDE2 inhibition during reperfusion and ischemia resulted in a specific increase in mitochondrial cAMP content, improved cell survival and accelerated recovery of cytosolic Ca 2+ homeostasis [ 184 ].…”

Section: Role Of Pde2 In Cardiovascular Diseasementioning

confidence: 99%

Therapeutic Implications for PDE2 and cGMP/cAMP Mediated Crosstalk in Cardiovascular Diseases

Sadek

Cachorro

El‐Armouche

et al. 2020

IJMS

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Phosphodiesterases (PDEs) are the principal superfamily of enzymes responsible for degrading the secondary messengers 3′,5′-cyclic nucleotides cAMP and cGMP. Their refined subcellular localization and substrate specificity contribute to finely regulate cAMP/cGMP gradients in various cellular microdomains. Redistribution of multiple signal compartmentalization components is often perceived under pathological conditions. Thereby PDEs have long been pursued as therapeutic targets in diverse disease conditions including neurological, metabolic, cancer and autoimmune disorders in addition to numerous cardiovascular diseases (CVDs). PDE2 is a unique member of the broad family of PDEs. In addition to its capability to hydrolyze both cAMP and cGMP, PDE2 is the sole isoform that may be allosterically activated by cGMP increasing its cAMP hydrolyzing activity. Within the cardiovascular system, PDE2 serves as an integral regulator for the crosstalk between cAMP/cGMP pathways and thereby may couple chronically adverse augmented cAMP signaling with cardioprotective cGMP signaling. This review provides a comprehensive overview of PDE2 regulatory functions in multiple cellular components within the cardiovascular system and also within various subcellular microdomains. Implications for PDE2- mediated crosstalk mechanisms in diverse cardiovascular pathologies are discussed highlighting the prospective use of PDE2 as a potential therapeutic target in cardiovascular disorders.

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Protective role of soluble adenylyl cyclase against reperfusion-induced injury of cardiac cells

Abstract: sAC plays an essential role in supporting cardiomyocytes viability during reperfusion. Elevation of mitochondrial cAMP pool either by sAC overexpression or by PDE2 inhibition beneficially affects cardiomyocyte survival during reperfusion.

Cited by 12 publications

References 29 publications

Functional Significance of the Adcy10-Dependent Intracellular cAMP Compartments

Functional Significance of the Adcy10-Dependent Intracellular cAMP Compartments

Therapeutic Implications for PDE2 and cGMP/cAMP Mediated Crosstalk in Cardiovascular Diseases

Therapeutic Implications for PDE2 and cGMP/cAMP Mediated Crosstalk in Cardiovascular Diseases

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