Table 2.

Cell Culture and Animal Studies Examining the Role of Gα_i/o in Apoptosis

No.	G Protein	Model System	Cell Type	Apoptotic Stimulus	Phenotype	Pathway	Comments	Ref.
1	Gαi	Endogenous CD47-stimulation	T Lymphocytes (Human CD4+/CD8- Jurkat T cells)	NONE	Stimulated	Inhibition of cAMP/PKA	CD47 is also known as Integrin-associated Protein	[66]
2	Gαi	Endogenous CD47-stimulation	Breast carcinoma cells	NONE	Stimulated	Inhibition of cAMP/PKA	CD47 is also known as Integrin-associated Protein	[67]
3	Gαi	Endogenous- Mastoparam activation	Macrophages (murine bone marrow derived)	NONE	Stimulated	Induced PI3K, PBK, and acid Sphingomyelinase pathways Induced NF-κB nuclear translocation		[68]
4	Q205LGαi2	Overexpression	Neurons (Human SH-SY5Y neuroblastoma cells	H2O2	Stimulated	Induction of BAK Activation of PARP		[47]
5	Gαi2	Endogenous Adenosine analog activation	Neurons (Human SH-SY5Y neuroblastoma cells	H2O2	Stimulated	Induction of BAK Activation of PARP		[47]
6	Gαi	Endogenous Clonidine, Norepinephrine (α2-adrenergic agonists)	Melanocytes (Oryzias latipes skin derived)	NONE	Stimulated	Inhibition of cAMP/PKA	Inhibited by Yohimbine, an α2-adrenergic receptor antagonist	[69]
7	Gαi	Endogenous LHRH (GnRH) activation	endometrial and ovarian adenocarcinomas	NONE	Stimulated	activation of phosphotyrosine phosphatase		[70]
8	Gαi	Endogenous GnRH (LHRH) and antagonist activation	Hormone Dependent Cancers (JEG-3, BPH-1)	NONE	Stimulated	Activation of JNK and p38	Specific to GnRH receptor type I; both agonists and antagonists activate Gαi	[71]
9	Gαi	Endogenous LPA-stimulated	Enterocytes (rat IEC-6 cells)	serum withdrawal campothecin TNF-α γ-irradiation	Inhibited	Induced ERK1/2 and Akt phosphorylation increased Bcl-2 expression		[72,73]
10	Gαi	Endogenous LPA-stimulated	T Lymphocytes (Human CD4+/CD8+/CD3low Tsup-1 cells)	Stimulation of FAS, CD2, CD3, and CD28	Inhibited	Suppression of BAX expression	models apoptosis induced by thymic selection	[75]
11	Gαi	Endogenous LPA-stimulated	Fibroblasts		Inhibited	MAPK, PI3K and Akt activation inhibition of downstream Caspase-9 activation		[74,75]
12	Gαi	Endogenous LPA-stimulated	Cardiomyocytes	Ischemia-reperfusion injury	Inhibited	Possibly IGF and calpain mediated	Ischemia induces necrosis; reperfusion induces apoptosis	[76]
13	Gαi	Endogenous LPA-stimulated	Hepatocytes (murine AML12 cells)	Clostridium difficile toxin TNF-α D-galactosamine	Inhibited	ERK1/2, PI3K, and Akt activation		[78]
14	Gαi	Endogenous LPA-stimulated	Cancer-derived (HeLa, DLD-1, HOS, Mcf-7 cell lines)	TRAILactivation	Inhibited	PI3K and Akt activation Induction of cFLIP Phosphorylation of BAD		[77]
15	Gαi	Endogenous S1P-stimulated	T Lymphocytes (Human CD4+/CD8+/CD3low Tsup-1 cells)	C6 ceramide	Inhibited	Suppression of BAX expression	models apoptosis induced by thymic selection	[75]
16	Gαi	Endogenous S1P-stimulated	Hepatocytes (rat hepatoma HTC4 cells)	Serum starvation	Inhibited	ERK1/2 activation	Possibly mediated by Rho activation	[79,80]
17	Gαi	Endogenous C-peptide stimulated	Renal Proximal Tubule Cells (opossum OK cells)	TNF-α	Inhibited	PI3K activation Activation of NF-κB	A Potential Model for Diabetic Nephropathy	[81]
18	Gαi	Endogenous T. Gondii infection stimulated	Macrophages (murine)	Staurosporine	Inhibited	PI3K activation ERK1/2 and Akt activation Downregulation of PARP		[82]
19	Gαi	Endogenous DHEA stimulated	Endothelial Cells (Bovine BAEC cells)	Serum starvation	Inhibited	PI3K/Akt activation Upregulation of Bcl-2	A Potential Atherosclerosis Model	[85]
20	Gαi	NGF UK14304	Neurons (rat PC12 cells)	None	Inhibited	PI3K/Akt activation Phorphorylation of BAD	May also be Gβγ mediated	[86]
21	Gαi	Endogenous β2-adrenergic receptor activation	Cardiomyocytes (murine primary cultures)		Inhibited	PI3K/Akt activation	β1-knockout Also pro-apoptotic through the actions of Gαs	[48]
22	Gαi	Endogenous β2-adrenergic receptor activation	Cardiomyocytes (rat primary cultures)	Hypoxia	Inhibited	PI3K/Akt activation	β1-blockade using CGP 20712A	[87,88]
23	Gαo	Endogenous	Neurons (mouse-rat FC11 cells)	Expression of mutant γ-secretase	Stimulated	Caspase-3 activation	Alzheimer’s Disease model	[90]
24	Gαo	Endogenous	Neurons (rat PC12 cells)	Serum withdrawal β-amyloid	Stimulated		Alzheimer’s Disease model	[91]