Acidosis promotes cell apoptosis through the G protein‑coupled receptor 4/CCAAT/enhancer‑binding protein homologous protein pathway

Dong, Biao; Zhang, Xiaolu; Fan, Yafeng; Cao, Shengli; Zhang, Xuepei

doi:10.3892/ol.2018.9478

Cited by 5 publications

(5 citation statements)

References 24 publications

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“…28 In addition, a recent study suggested that acidemia can promote cell apoptosis through the G protein-coupled receptor 4/ CCAAT/enhancer-binding protein homologous protein pathway. 29 A previous research demonstrated that the expression of miR-133b, which is involved in the regulation of proliferation, cell death and migration can be regulated by acidemia. 30 In the present study, the 30-day mortality and 90-day mortality of AMI patients with acidemia were higher than the AMI patients without acidemia.…”

Section: Discussionmentioning

confidence: 99%

Association of Acidemia With Short-Term Mortality of Acute Myocardial Infarction: A Retrospective Study Base on MIMIC-III Database

Zhang

Guan

Líu

2020

Clin Appl Thromb Hemost

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Acute myocardial infarction (AMI) is a leading cause of death and not a few of these patients are combined with acidemia. This study aimed to detect the association of acidemia with short-term mortality of AMI patients. A total of 972 AMI patients were selected from the Medical Information Mart for Intensive Care (MIMIC) III database for analysis. Propensity-score matching (PSM) was used to reduce the imbalance. Kaplan-Meier survival analysis was used to compare the mortality, and Cox-proportional hazards model was used to detect related factors associated with mortality. After PSM, a total of 345 non-acidemia patients and 345 matched acidemia patients were included. The non-acidemia patients had a significantly lower 30-day mortality (20.0% vs. 28.7%) and lower 90-day mortality (24.9% vs. 31.9%) than the acidemia patients ( P < 0.001 for all). The severe-acidemia patients (PH < 7.25) had the highest 30-day mortality (52.6%) and 90-day mortality (53.9%) than non-acidemia patients and mild-acidemia (7.25 ≤ PH < 7.35) patients ( P < 0.001). In Cox-proportional hazards model, acidemia was associated with improved 30-day mortality (HR = 1.518; 95%CI = 1.110-2.076, P = 0.009) and 90-day mortality (HR = 1.378; 95%CI = 1.034 -1.837, P = 0.029). These results suggest that severe acidemia is associated with improved 30-day mortality and 90-day mortality of AMI patients.

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Section: Discussionmentioning

confidence: 99%

Association of Acidemia With Short-Term Mortality of Acute Myocardial Infarction: A Retrospective Study Base on MIMIC-III Database

Zhang

Guan

Líu

2020

Clin Appl Thromb Hemost

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“…Activation of GPR4 by extracellular acidification also increase the expression of chemokines, cytokines, and adhesion molecules through the NF-kB pathway in endothelial cells (Table 1) (176)(177)(178). Acidosis-induced activation of GPR4 promotes the endoplasmic reticulum (ER) stress response and apoptosis of endothelial cells (177,179,180). GPR4 -/reduces inflammation in the DSS-induced acute colitis and in the spontaneous IL-10-/-colitis model in rodents (169,181).…”

Section: Gaq/ 11 and Gasmentioning

confidence: 99%

Role of Lactate in Inflammatory Processes: Friend or Foe

et al. 2022

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During an inflammatory process, shift in the cellular metabolism associated with an increase in extracellular acidification are well-known features. This pH drop in the inflamed tissue is largely attributed to the presence of lactate by an increase in glycolysis. In recent years, evidence has accumulated describing the role of lactate in inflammatory processes; however, there are differences as to whether lactate can currently be considered a pro- or anti-inflammatory mediator. Herein, we review these recent advances on the pleiotropic effects of lactate on the inflammatory process. Taken together, the evidence suggests that lactate could exert differential effects depending on the metabolic status, cell type in which the effects of lactate are studied, and the pathological process analyzed. Additionally, various targets, including post-translational modifications, G-protein coupled receptor and transcription factor activation such as NF-κB and HIF-1, allow lactate to modulate signaling pathways that control the expression of cytokines, chemokines, adhesion molecules, and several enzymes associated with immune response and metabolism. Altogether, this would explain its varied effects on inflammatory processes beyond its well-known role as a waste product of metabolism.

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“…Activation of GPR4 by acidosis stimulates the expression of inflammatory chemokines, cytokines, adhesion molecules and the NF-κB pathway in endothelial cells, increases endothelium-leukocyte adhesion, and facilitates leukocyte infiltration (11)(12)(13)(14)(15)(16)20). Moreover, activation of GPR4 by acidosis promotes the endoplasmic reticulum (ER) stress response and apoptosis of endothelial cells (12,13,33).…”

Section: Evaluation Of the Hypothesismentioning

confidence: 99%

Can GPR4 Be a Potential Therapeutic Target for COVID-19?

et al. 2021

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Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first emerged in late 2019 and has since rapidly become a global pandemic. SARS-CoV-2 infection causes damages to the lung and other organs. The clinical manifestations of COVID-19 range widely from asymptomatic infection, mild respiratory illness to severe pneumonia with respiratory failure and death. Autopsy studies demonstrate that diffuse alveolar damage, inflammatory cell infiltration, edema, proteinaceous exudates, and vascular thromboembolism in the lung as well as extrapulmonary injuries in other organs represent key pathological findings. Herein, we hypothesize that GPR4 plays an integral role in COVID-19 pathophysiology and is a potential therapeutic target for the treatment of COVID-19. GPR4 is a pro-inflammatory G protein-coupled receptor (GPCR) highly expressed in vascular endothelial cells and serves as a “gatekeeper” to regulate endothelium-blood cell interaction and leukocyte infiltration. GPR4 also regulates vascular permeability and tissue edema under inflammatory conditions. Therefore, we hypothesize that GPR4 antagonism can potentially be exploited to mitigate the hyper-inflammatory response, vessel hyper-permeability, pulmonary edema, exudate formation, vascular thromboembolism and tissue injury associated with COVID-19.

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Acidosis promotes cell apoptosis through the G protein‑coupled receptor 4/CCAAT/enhancer‑binding protein homologous protein pathway

Cited by 5 publications

References 24 publications

Association of Acidemia With Short-Term Mortality of Acute Myocardial Infarction: A Retrospective Study Base on MIMIC-III Database

Association of Acidemia With Short-Term Mortality of Acute Myocardial Infarction: A Retrospective Study Base on MIMIC-III Database

Role of Lactate in Inflammatory Processes: Friend or Foe

Can GPR4 Be a Potential Therapeutic Target for COVID-19?

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