Brain Gαi2-subunit proteins and the prevention of salt sensitive hypertension

Carmichael, Casey Y.; Wainford, Richard D.

doi:10.3389/fphys.2015.00233

Cited by 3 publications

(3 citation statements)

References 94 publications

(156 reference statements)

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“…To accomplish this goal, we first confirmed that 5-HT2C receptor expression was present in rat hippocampal neurons within the DG region. It has been reported that inhibitory G protein-coupled receptors play a key role in regulating the central and peripheral nervous systems [ 49 , 50 ]. Gαi-2 was shown to block the transient inhibition of mGluR2 on synaptic transmission and enhances LTD [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Agomelatine rescues lipopolysaccharide-induced neural injury and depression-like behaviors via suppression of the Gαi-2-PKA-ASK1 signaling pathway

Lan

Zhang

et al. 2022

J Neuroinflammation

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Background Agomelatine has been shown to be effective in the treatment of depression, but the molecular mechanisms underlying its antidepressant effects have yet to be elucidated. Identification of these molecular mechanisms would not only offer new insights into the basis for depression but also provide the foundation for the development of novel treatments for this disorder. Methods Intraperitoneal injection of LPS was used to induce depression-like behaviors in rats. The interactions of the 5-HT2C reporter and Gαi-2 were verified by immunoprecipitation or immunofluorescence assay. Inflammatory related proteins, autophagy related proteins and apoptosis markers were verified by immunoblotting or immunofluorescence assay. Finally, electron microscopy analysis was used to observe the synapse and ultrastructural pathology. Results Here, we found that the capacity for agomelatine to ameliorate depression and anxiety in a lipopolysaccharide (LPS)-induced rat model of depression was associated with an alleviation of neuroinflammation, abnormal autophagy and neuronal apoptosis as well as the promotion of neurogenesis in the hippocampal dentate gyrus (DG) region of these rats. We also found that the 5-HT2C receptor is coupled with G alphai (2) (Gαi-2) protein within hippocampal neurons and, agomelatine, acting as a 5-HT2C receptor antagonist, can up-regulate activity of the Gαi-2-cAMP-PKA pathway. Such events then suppress activation of the apoptosis signal-regulating kinase 1 (ASK1) pathway, a member of the mitogen-activated protein kinase (MAPK) family involved in pathological processes of many diseases. Conclusion Taken together, these results suggest that agomelatine plays a neuroprotective role in regulating neuroinflammation, autophagy disorder and apoptosis in this LPS-induced rat model of depression, effects which are associated with the display of antidepressant behaviors. These findings provide evidence for some of the potential mechanisms for the antidepressant effects of agomelatine. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Agomelatine rescues lipopolysaccharide-induced neural injury and depression-like behaviors via suppression of the Gαi-2-PKA-ASK1 signaling pathway

Lan

Zhang

et al. 2022

J Neuroinflammation

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“…The PI3K-Akt Pathway activation has been implicated to contribute to the progression of atherosclerotic plaque formation and pathological changes in the vasculature leading to hypertension and cardiovascular disorders in many studies ( 171 – 175 ). Several other cellular pathways associated with salt sensitive hypertension such as the WNK signaling pathway ( 176 ), Kelch-like 3/Cullin 3 ubiquitin ligase complex ( 177 ), brain Gαi2-proteins of GPCR ( 178 , 179 ) in the central nervous system, MAPK/extracellular signal regulated kinase [ERK] mediated by angiotensin II in vascular smooth muscles ( 180 ), and redox signaling ( 181 ) have been well elucidated.…”

Section: Dietary Salt In Hypertensive Heart Disease and Its Complicat...mentioning

confidence: 99%

Hypertensive heart disease: risk factors, complications and mechanisms

Masenga

Kirabo

2023

Front. Cardiovasc. Med.

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Hypertensive heart disease constitutes functional and structural dysfunction and pathogenesis occurring primarily in the left ventricle, the left atrium and the coronary arteries due to chronic uncontrolled hypertension. Hypertensive heart disease is underreported and the mechanisms underlying its correlates and complications are not well elaborated. In this review, we summarize the current understanding of hypertensive heart disease, we discuss in detail the mechanisms associated with development and complications of hypertensive heart disease especially left ventricular hypertrophy, atrial fibrillation, heart failure and coronary artery disease. We also briefly highlight the role of dietary salt, immunity and genetic predisposition in hypertensive heart disease pathogenesis.

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“…G protein-coupled receptors activate heterotrimeric G proteins via ligand binding, thereby modulating the activity of cellular effectors and consequently regulating a wide array of cell functions 1 2 . The putative function of the functional class of G protein Gαi is defined by their ability to downregulate cAMP levels by inhibition of adenylyl cyclase 2 3 .…”

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confidence: 99%

Blunted apoptosis of erythrocytes in mice deficient in the heterotrimeric G-protein subunit Gαi2

Bissinger

Lang

Ghashghaeinia

et al. 2016

Sci Rep

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Putative functions of the heterotrimeric G-protein subunit Gαi2-dependent signaling include ion channel regulation, cell differentiation, proliferation and apoptosis. Erythrocytes may, similar to apoptosis of nucleated cells, undergo eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine (PS) exposure. Eryptosis may be triggered by increased cytosolic Ca2+ activity and ceramide. In the present study, we show that Gαi2 is expressed in both murine and human erythrocytes and further examined the survival of erythrocytes drawn from Gαi2-deficient mice (Gαi2−/−) and corresponding wild-type mice (Gαi2+/+). Our data show that plasma erythropoietin levels, erythrocyte maturation markers, erythrocyte counts, hematocrit and hemoglobin concentration were similar in Gαi2−/− and Gαi2+/+ mice but the mean corpuscular volume was significantly larger in Gαi2−/− mice. Spontaneous PS exposure of circulating Gαi2−/− erythrocytes was significantly lower than that of circulating Gαi2+/+ erythrocytes. PS exposure was significantly lower in Gαi2−/− than in Gαi2+/+ erythrocytes following ex vivo exposure to hyperosmotic shock, bacterial sphingomyelinase or C6 ceramide. Erythrocyte Gαi2 deficiency further attenuated hyperosmotic shock-induced increase of cytosolic Ca2+ activity and cell shrinkage. Moreover, Gαi2−/− erythrocytes were more resistant to osmosensitive hemolysis as compared to Gαi2+/+ erythrocytes. In conclusion, Gαi2 deficiency in erythrocytes confers partial protection against suicidal cell death.

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Brain Gαi2-subunit proteins and the prevention of salt sensitive hypertension

Cited by 3 publications

References 94 publications

Agomelatine rescues lipopolysaccharide-induced neural injury and depression-like behaviors via suppression of the Gαi-2-PKA-ASK1 signaling pathway

Agomelatine rescues lipopolysaccharide-induced neural injury and depression-like behaviors via suppression of the Gαi-2-PKA-ASK1 signaling pathway

Hypertensive heart disease: risk factors, complications and mechanisms

Blunted apoptosis of erythrocytes in mice deficient in the heterotrimeric G-protein subunit Gαi2

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