G protein-coupled receptor systems and their lipid environment in health disorders during aging

Abstract

Cells, tissues and organs undergo phenotypic changes and deteriorate as they age. Cell growth arrest and hyporesponsiveness to extrinsic stimuli are all hallmarks of senescent cells. Most such external stimuli received by a cell are processed by two different cell membrane systems: receptor tyrosine kinases (RTKs) and G protein-coupled receptors (GPCRs). GPCRs form the largest gene family in the human genome and they are involved in most relevant physiological functions. Given the changes observed in the expression and activity of GPCRs during aging, it is possible that these receptors are directly involved in aging and certain age-related pathologies. On the other hand, both GPCRs and G proteins are associated with the plasma membrane and since lipid-protein interactions regulate their activity, they can both be considered to be sensitive to the lipid environment. Changes in membrane lipid composition and structure have been described in aged cells and furthermore, these membrane changes have been associated with alterations in GPCR mediated signaling in some of the main health disorders in elderly subjects. Although senescence could be considered a physiologic process, not all aging humans develop the same health disorders. Here, we review the involvement of GPCRs and their lipid environment in the development of the major human pathologies associated with aging such as cancer, neurodegenerative disorders and cardiovascular pathologies.

G protein-coupled receptor-receptor interactions give integrative dynamics to intercellular communication

“…In this respect, the first aspect deserving consideration is the lipid environment. It was shown to influence GPCR function and several health disorders during aging were assigned to changes in the membrane composition that altered GPCR signaling (Alemany et al, 2007). The preferential localization of GPCR and other components involved in signal propagation in dynamic membrane nano domains (lipid rafts and caveolae) has been reported in a vast number of studies (Insel et al, 2005;Lingwood and Simons, 2010;Simons and Sampaio, 2011).…”

Oleic acid content is responsible for the reduction in blood pressure induced by olive oil

“…In a study of a human population with controlled diets, which only varied in the type of oil used, VOO induced marked and significant reductions in BP with respect to sunflower seed oil (17). Numerous studies suggest that this and other beneficial effects of VOO on cardiovascular health are caused by minor components present in this oil (23).…”

“…Long-term intake of high doses of VOO reduces BP and the risk of developing hypertension (13)(14)(15)(16). At the molecular level, OA and VOO regulate G protein-associated signaling both in vivo (in humans) and in cell culture (1,17). Interestingly, the hypotensive effect of 2-hydroxyoleic acid involves changes in the same signaling pathways as those affected by OA (18,19).…”

Cellular modelling: experiments and simulation to develop a physiological model of G-protein control of muscarinic K + channels in mammalian atrial cells

“…Defects in the expression and regulation of GPCRs and/or G-proteins underlie various cardiovascular defects and diseases (Smith & Luttrell 2006;Alemany et al 2007), contributing to heart failure (Meij 1996;Feldman et al 2008) and cardiac hypertrophy (Akhter et al 1998;Sakata et al 1998;Barry et al 2008). The G-protein signalling pathways are therefore regarded as therapy targets for cardiovascular diseases and their characteristics need to be understood quantitatively (Alemany et al 2007).…”

“…Defects in the expression and regulation of GPCRs and/or G-proteins underlie various cardiovascular defects and diseases (Smith & Luttrell 2006;Alemany et al 2007), contributing to heart failure (Meij 1996;Feldman et al 2008) and cardiac hypertrophy (Akhter et al 1998;Sakata et al 1998;Barry et al 2008). The G-protein signalling pathways are therefore regarded as therapy targets for cardiovascular diseases and their characteristics need to be understood quantitatively (Alemany et al 2007). Mathematical models of G-protein signalling can play an important role in developing quantitative understanding of these signalling pathways (Thomsen et al 1988;Mackay 1990;Felber et al 1996;Mosser et al 2002;Hao et al 2003;Saucerman et al 2003;Yi et al 2003;Zhong et al 2003;Suh et al 2004;Katanaev & Chornomorets 2007;Linderman 2009).…”