AI Article Synopsis
- - The study investigates how estrogen and the enzyme CD73 work together to protect the heart from damage during chronic stress, specifically examining their roles in myocardial injury.
- - Researchers used mice to assess the effects of estrogen on cardiac injury markers and other parameters after inducing stress with isoproterenol, finding that estrogen deficiency worsens heart damage by activating the CD73/adenosine pathway.
- - It was concluded that estrogen helps to normalize this pathway through the PI3K/Akt signaling pathway, offering insight into its cardioprotective mechanisms during stressful conditions.
Article Abstract
Background: During myocardial damage, the sex hormone estrogen and CD73, the main enzyme that converts AMP into adenosine, are cardioprotective molecules. However, it is unclear how these two molecules work together to provide cardioprotection. The current study aimed to elucidate the interaction between estrogen and CD73 under chronic stress.
Methods: Ovariectomy and SHAM operations were done on FVB wild-type (WT) female mice. Two weeks after the operation, the mice were treated with daily isoproterenol (10 mg/kg/day) injections for 14 days. The effect of E2 on relevant cardiac injury biomarkers (BNP, ANP), myocardial morphology (cardiomyocyte surface area), electrocardiography, CD73 protein expression and activity, and macrophage (CD86 + and CD206 +) infiltrations were assessed. In vitro, H9C2 cells were treated with 1 nM of estrogen and 10 mM APCP (CD73 inhibitor α, β-methylene adenosine-5'-diphosphate), 10 µM isoproterenol and 20 µm LY294002 (PI3K inhibitor) for 24 h and western blot was done to elucidate the mechanism behind the effect of estrogen on the CD73/adenosine axis.
Results: Estrogen deficiency during chronic catecholamine stress caused myocardial injury, thereby triggering the hyperactivity of the CD73/adenosine axis, which aggravated myocarditis, adverse remodeling, and arrhythmias. However, estrogen normalizes CD73/Adenosine axis via the upregulation of PI3K/Akt pathways to prevent adverse outcomes during stress. In vivo results showed that the inhibition of PI3K significantly decreased PI3K/Akt pathways while upregulating the CD73/adenosine axis and apoptosis.
Conclusion: Estrogen's pleiotropy cardioprotection mechanism during stress includes its normalization of the CD73/Adenosine axis via the PI3K/Akt pathway. Video Abstract.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9948346 | PMC |
| http://dx.doi.org/10.1186/s12964-023-01052-0 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Adenosine signaling in tumor-associated macrophages and targeting adenosine signaling for cancer therapy.
Cancer Biol Med
December 2024
Biotherapy Center and Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
This review examined the critical role of adenosine signaling in modulating the behavior of tumor-associated macrophages (TAMs), a key determinant of the tumor microenvironment (TME). Adenosine is an immunosuppressive metabolite that is highly enriched in the TME due to elevated expression of adenosine triphosphatase (ATPase). Adenosine influences polarization of TAMs through A2A and A2B receptors, which drives a phenotype that supports tumor progression and immune evasion.
View Article and Find Full Text PDFKnock-out of CD73 delays the onset of HR-negative breast cancer by reprogramming lipid metabolism and is associated with increased tumor mutational burden.
Mol Metab
November 2024
Laboratory of Cell Biology and Immunology, Institute of Medical Biotechnology and Experimental Oncology, Intercollegiate Faculty of Biotechnology University of Gdańsk and Medical University of Gdańsk, Medical University of Gdańsk, Poland. Electronic address:
Objective: CD73 (ecto-5'-nucleotidase, NT5E), a cell-surface enzyme converting 5'-AMP to adenosine, is crucial for cancer progression. However, its role in the tumorigenesis process remains mostly obscure. We aimed to demonstrate CD73's role in breast cancer (BC) tumorigenesis through metabolic rewiring of fatty acid metabolism, a process recently indicated to be regulated by BC major prognostic markers, hormone receptors (HR) for estrogen (ER), and progesterone (PR).
View Article and Find Full Text PDFHuman placental mesenchymal stromal cells alleviate intestinal oxidative damage in mice with graft-versus-host disease via CD73/adenosine/PI3K/Akt/GSK-3β axis.
Cell Signal
November 2024
Department of Immunology, Binzhou Medical University, Yantai, 264000, Shandong Province, China. Electronic address:
Article Synopsis
- Human placental mesenchymal stromal cells (hPMSCs) help reduce intestinal damage in graft-versus-host disease (GVHD) by decreasing oxidative stress and improving tight junction protein expression.
- In experiments with GVHD mice and TNF-α-stimulated human colon cells, hPMSCs demonstrated a reduction in harmful substances and an increase in protective enzymes.
- The mechanisms behind hPMSCs' protective effects are linked to a specific signaling pathway involving CD73, adenosine, and several key proteins that regulate oxidative stress and cell integrity.
Hyperbaric Oxygen Attenuates Chronic Postsurgical Pain by Regulating the CD73/Adenosine/A1R Axis of the Spinal Cord in Rats.
J Pain
November 2024
Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Anesthesiology and Perioperative medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China. Electronic address:
Chronic postsurgical pain (CPSP) affects postoperative rehabilitation and quality of life in patients, but its mechanisms are still poorly understood. Hyperbaric oxygen (HBO) attenuates neuropathic pain in animal and human studies, but its efficacy for CPSP treatment and its underlying mechanism have not been elucidated. This study aimed to investigate the analgesic effect of HBO in a CPSP rat model and the role of spinal cord adenosine circulation in HBO-induced analgesia.
View Article and Find Full Text PDFFeedback activation of CD73-Adenosine axis attenuates the antitumor immunity of STING pathway.
Biochem Biophys Res Commun
May 2024
State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, 518055, China. Electronic address:
The cGAS-STING pathway, a crucial component of innate immunity, has garnered attention as a potential therapeutic target for tumor treatment, but targeting this pathway is complicated by diverse feedback mechanisms of the cGAS-STING pathway. In this study, we demonstrated that STING activation enhanced the expression of CD73 and the subsequent production of adenosine in immune cells and cancer cells. Mechanistically, the feedback activation of CD73 depended on the type I IFN/IFNAR axis induced by STING activation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!