scholarly journals The Constitutively Active Orphan G-protein-coupled Receptor GPR39 Protects from Cell Death by Increasing Secretion of Pigment Epithelium-derived Growth Factor

2008 ◽  
Vol 283 (11) ◽  
pp. 7074-7081 ◽  
Author(s):  
Sonja Dittmer ◽  
Mert Sahin ◽  
Anna Pantlen ◽  
Ambrish Saxena ◽  
Diamandis Toutzaris ◽  
...  
Keyword(s):  
Cell Death ◽  
Growth Factor ◽  
G Protein ◽  
Pigment Epithelium ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled ◽  
Constitutively Active

scholarly journals G Protein-coupled Receptor Kinase-mediated Desensitization of Metabotropic Glutamate Receptor 1A Protects against Cell Death

2000 ◽  
Vol 275 (49) ◽  
pp. 38213-38220 ◽  
Author(s):  
Lianne B. Dale ◽  
Moshmi Bhattacharya ◽  
Pieter H. Anborgh ◽  
Barbara Murdoch ◽  
Mickie Bhatia ◽  
...  
Keyword(s):  
Cell Death ◽  
G Protein ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
Metabotropic Glutamate ◽  
G Protein Coupled

scholarly journals GPR4 Knockout Improves the Neurotoxin-Induced, Caspase-Dependent Mitochondrial Apoptosis of the Dopaminergic Neuronal Cell

2020 ◽  
Vol 21 (20) ◽  
pp. 7517
Author(s):  
Md Ezazul Haque ◽  
Mahbuba Akther ◽  
Shofiul Azam ◽  
Dong-Kug Choi ◽  
In-Su Kim
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
G Protein ◽  
Apoptotic Cell ◽  
B Cell Lymphoma ◽  
Apoptotic Cell Death ◽  
G Protein Coupled Receptor ◽  
Human Neuroblastoma ◽  
G Protein Coupled

In Parkinson’s disease, mitochondrial oxidative stress-mediated apoptosis is a major cause of dopaminergic neuronal loss in the substantia nigra (SN). G protein-coupled receptor 4 (GPR4), previously recognised as an orphan G protein coupled-receptor (GPCR), has recently been claimed as a member of the group of proton-activated GPCRs. Its activity in neuronal apoptosis, however, remains undefined. In this study, we investigated the role of GPR4 in the 1-methyl-4-phenylpyridinium ion (MPP+) and hydrogen peroxide (H2O2)-treated apoptotic cell death of stably GPR4-overexpressing and stably GPR4-knockout human neuroblastoma SH-SY5Y cells. In GPR4-OE cells, MPP+ and H2O2 were found to significantly increase the expression levels of both mRNA and proteins of the pro-apoptotic Bcl-2-associated X protein (Bax) genes, while they decreased the anti-apoptotic B-cell lymphoma 2 (Bcl-2) genes. In addition, MPP+ treatment activated Caspase-3, leading to the cleavage of poly (ADP-ribose) polymerase (PARP) and decreasing the mitochondrial membrane potential (ΔΨm) in GPR4-OE cells. In contrast, H2O2 treatment significantly increased the intracellular calcium ions (Ca2+) and reactive oxygen species (ROS) in GPR4-OE cells. Further, chemical inhibition by NE52-QQ57, a selective antagonist of GPR4, and knockout of GPR4 by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 decreased the Bax/Bcl-2 ratio and ROS generation, and stabilised the ΔΨm, thus protecting the SH-SY5Y cells from MPP+- or H2O2-induced apoptotic cell death. Moreover, the knockout of GPR4 decreased the proteolytic degradation of phosphatidylinositol biphosphate (PIP2) and subsequent release of the endoplasmic reticulum (ER)-stored Ca2+ in the cytosol. Our results suggest that the pharmacological inhibition or genetic deletion of GPR4 improves the neurotoxin-induced caspase-dependent mitochondrial apoptotic pathway, possibly through the modulation of PIP2 degradation-mediated calcium signalling. Therefore, GPR4 presents a potential therapeutic target for neurodegenerative disorders such as Parkinson’s disease.

Human herpesvirus KSHV encodes a constitutively active G-protein-coupled receptor linked to cell proliferation

Nature ◽  
1997 ◽  
Vol 385 (6614) ◽  
pp. 347-350 ◽  
Author(s):  
Leandros Arvanitakis ◽  
Elizabeth Geras-Raaka ◽  
Anjali Varma ◽  
Marvin C. Gershengorn ◽  
Ethel Cesarman
Keyword(s):  
Cell Proliferation ◽  
G Protein ◽  
Human Herpesvirus ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled ◽  
Constitutively Active
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