. 2023 Jun 19;14:1207280. doi: 10.3389/fphys.2023.1207280

TABLE 1.

Studies of cAMP modulators in in vitro models of regulated cell deaths.

Research	Regulated cell deaths	cAMP modulators	Target	Model	Main research findings
Brunyanszki et al. (2014)	Parthanatos	Propranolol	β-receptor antagonist	U937	β -adrenoceptor/cAMP/PKA axis phosphorylates PARP-1 subsequently leading to parthanatos
		DDA	AC inhibitor	C2C12
		PKAi	PKA inhibitor
		Isoproterenol	β-receptor agonist
		Forskolin	AC activator
		8-Br-cAMP	PKA&Epac activator
Grandoch et al. (2009a)	Parthanatos	8-pCPT-2′-O-Me-cAMP	Epac activator	U937	Epac activation leads to inhibition of PARP cleavage
Grandoch et al. (2009b)	Parthanatos	8-Br-cAMP	PKA&Epac activator	WEHI 231	Epac upregulates PARP expression via Rap1 and H-Ras
		dd-Ado	AC inhibitor
		SQ22536	AC inhibitor
		H-89	PKA inhibitor
		Forskolin	AC activator
		Rp-8CPT-cAMP	PKA inhibitor
		8-pCPT-2′-O-MecAMP	Epac activator
Bokoch et al. (2009)	Netosis	H-89	PKA inhibitor	HEK293	NOXA1 phosphorylation by PKA recruits 14-3-3 protein subsequently inhibiting Nox holoenzyme assembly and potentially preventing netosis
Bokoch et al. (2009)	Netosis	Forskolin	AC activator	HT-29
Eby et al. (2014)	Netosis	Forskolin	AC activator pan-PDE inhibitor	Neutrophil	Elevated cAMP by AC inhibits NETs formation and oxidative burst
Eby et al. (2014)	Netosis	IBMX	AC activator pan-PDE inhibitor	Neutrophil
Stahl-Meyer et al. (202)	Lysosome dependent cell death	Forskolin	AC activator	MCF7	Lysosphingolipid-induced lysosome-dependent cell death requires cAMP signaling seemingly sensitizing cells to lysosome-dependent cell death
Stahl-Meyer et al. (202)	Lysosome dependent cell death	Forskolin	AC activator	Fibroblast
Sung et al. (2020)	Senescence	H-89	PKA inhibitor	Vascular smooth muscle cell	cAMP/PKA-SIRT1 seem to mediate antisenescence mechanisms
Sung et al. (2020)	Senescence	Forskolin	AC activator	Vascular smooth muscle cell	cAMP/PKA-SIRT1 seem to mediate antisenescence mechanisms
Wang et al. (2022)	Senescence	Forskolin	AC activator	mesenchymal stem cells	cAMP alterations impact senescence and senescence-related inflammatory phenotypes
Wang et al. (2022)	Senescence	SQ22536	AC inhibitor	mesenchymal stem cells
Ishii et al. (2019)	Ferroptosis	8-Br-cAMP	PKA&Epac activator	Yeast mitochondria	PKA suppresses mitochondria and indirectly inhibits Nrf2
Musheshe et al. (2022)	Ferroptosis	CE3F4	Epac1 inhibitor	HT-22	Epac1 inhibition reduces ROS and lipid peroxidation subsequently preventing ferroptosis
		ESI-05	Epac2 inhibitor
		ESI-09	Epac inhibitor
		8-pCPT-2′-O-Me-cAMP	Epac activator

AC, adenylyl cyclase; DDA, 2′,3′-dideoxyadenosine; PKA, protein kinase A; epac, exchange protein directly activated by cAMP; IBMX, 3-isobutyl-1-methylxanthine; PARP, Poly (ADP-ribose) polymerase; Nox, NADPH oxidase; NETs, neutrophil extracellular traps; SIRT1, Sirtuin 1; Nrf2, nuclear factor erythroid 2-related factor 2.