title: Recent Advances on the Role of G Protein-Coupled Receptors in Hypoxia-Mediated Signaling.
abstract: G protein-coupled receptors (GPCRs) are cell surface proteins mainly involved in signal transmission; however, they play a role also in several pathophysiological conditions. Chemically heterogeneous molecules like peptides, hormones, lipids, and neurotransmitters activate second messengers and induce several biological responses by binding to these seven transmembrane receptors, which are coupled to heterotrimeric G proteins. Recently, additional molecular mechanisms have been involved in GPCR-mediated signaling, leading to an intricate network of transduction pathways. In this regard, it should be mentioned that diverse GPCR family members contribute to the adaptive cell responses to low oxygen tension, which is a distinguishing feature of several illnesses like neoplastic and cardiovascular diseases. For instance, the G protein estrogen receptor, namely G protein estrogen receptor (GPER)/GPR30, has been shown to contribute to relevant biological effects induced by hypoxia via the hypoxia-inducible factor (HIF)-1α in diverse cell contexts, including cancer. Likewise, GPER has been found to modulate the biological outcome of hypoxic/ischemic stress in both cardiovascular and central nervous systems. Here, we describe the role exerted by GPCR-mediated signaling in low oxygen conditions, discussing, in particular, the involvement of GPER by a hypoxic microenvironment.
authors: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via Bucci, 87036, Rende, CS, Italy.
authors: Rosamaria
authors: R
authors: Lappano
authors: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via Bucci, 87036, Rende, CS, Italy.
authors: Damiano
authors: D
authors: Rigiracciolo
authors: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via Bucci, 87036, Rende, CS, Italy.
authors: Paola
authors: P
authors: De Marco
authors: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via Bucci, 87036, Rende, CS, Italy.
authors: Silvia
authors: S
authors: Avino
authors: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via Bucci, 87036, Rende, CS, Italy.
authors: Anna Rita
authors: AR
authors: Cappello
authors: UOS Proteomics IRCCS AOU San Martino-IST National Institute for Cancer Research, Largo R. Benzi 10, 16132, Genoa, Italy.
authors: Camillo
authors: C
authors: Rosano
authors: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via Bucci, 87036, Rende, CS, Italy. marcellomaggiolini@yahoo.it.
authors: Marcello
authors: M
authors: Maggiolini
authors: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via Bucci, 87036, Rende, CS, Italy.
authors: Ernestina Marianna
authors: EM
authors: De Francesco
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D020533:Angiogenesis Inhibitors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D043562:Receptors, G-Protein-Coupled
keywords: GPCRs; GPER; angiogenesis; hypoxia; signal transduction