ArticleJournal of cellular and molecular medicine2017
Zinc rescues obesity-induced cardiac hypertrophy via stimulating metallothionein to suppress oxidative stress-activated BCL10/CARD9/p38 MAPK pathway.
Article in Journal of cellular and molecular medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 53 citations in OpenAlex.
- Zinc Attenuates Cadmium and High-Fat Diet-Induced Cardiomyopathy by Enhancing Metallothionein-Mediated Cardiac Protection.Biological trace element research · 2026Article
- Zinc and animal health: an in-depth exploration of its role in physiological functions and regulatory molecular mechanisms.Journal of animal science and biotechnology · 2025Review
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- New insights into the role of metallothioneins in obesity and diabetes.International journal of obesity (2005) · 2025Review
- ANP Increases ZnCurrent medical science · 2025Article
- Exacerbation by knocking-out metallothionein gene of obesity-induced cardiac remodeling is associated with the activation of CARD9 signaling.International journal of biological sciences · 2025Article
- Macrophage OTUD1-CARD9 axis drives isoproterenol-induced inflammatory heart remodelling.Clinical and translational medicine · 2024Article
- Supplementation of Micro- and Macronutrients-A Role of Nutritional Status in Non-Alcoholic Fatty Liver Disease.International journal of molecular sciences · 2024Review
- Metabolite, immunocyte phenotype, and lymphoma: a Mendelian randomization study.Frontiers in immunology · 2024Article
- Regulatory roles of CARD9-BCL10-Rac1 (CBR) signalome in islet β-cell function in health and metabolic stress: Is there room for MALT1?Biochemical pharmacology · 2023Review
- Metal-Binding Proteins Cross-Linking with Endoplasmic Reticulum Stress in Cardiovascular Diseases.Journal of cardiovascular development and disease · 2023Review
- Metallothionein-2A Protects Cardiomyocytes from Hypoxia/reper-Fusion through Inhibiting p38.Cell biochemistry and biophysics · 2023Article
- CARD9 deficiency improves the recovery of limb ischemia in mice with ambient fine particulate matter exposure.Frontiers in cardiovascular medicine · 2023Article
- Direct cardio-protection of Dapagliflozin against obesity-related cardiomyopathy via NHE1/MAPK signaling.Acta pharmacologica Sinica · 2022Article
- Anti-Diabetic Therapy, Heart Failure and Oxidative Stress: An Update.Journal of clinical medicine · 2022Review
- EGR1 Is Implicated in Right Ventricular Cardiac Remodeling Associated with Pulmonary Hypertension.Biology · 2022Article
- CARD9 Mediates Pancreatic Islet Beta-Cell Dysfunction Under the Duress of Hyperglycemic Stress.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2022Article
- Sex differences in the effects of whole-life, low-dose cadmium exposure on postweaning high-fat diet-induced cardiac pathogeneses.The Science of the total environment · 2022Article
- CARD9 Signaling, Inflammation, and Diseases.Frontiers in immunology · 2022Review
- CARD9 Regulation and its Role in Cardiovascular Diseases.International journal of biological sciences · 2022Review
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Obesity often leads to obesity-related cardiac hypertrophy (ORCH), which is suppressed by zinc-induced inactivation of p38 mitogen-activated protein kinase (p38 MAPK). In this study, we investigated the mechanisms by which zinc inactivates p38 MAPK to prevent ORCH. Mice (4-week old) were fed either high fat diet (HFD, 60% kcal fat) or normal diet (ND, 10% kcal fat) containing variable amounts of zinc (deficiency, normal and supplement) for 3 and 6 months. P38 MAPK siRNA and the p38 MAPK inhibitor SB203580 were used to suppress p38 MAPK activity in vitro and in vivo, respectively. HFD activated p38 MAPK and increased expression of B-cell lymphoma/CLL 10 (BCL10) and caspase recruitment domain family member 9 (CARD9). These responses were enhanced by zinc deficiency and attenuated by zinc supplement. Administration of SB203580 to HFD mice or specific siRNA in palmitate-treated cardiomyocytes eliminated the HFD and zinc deficiency activation of p38 MAPK, but did not significantly impact the expression of BCL10 and CARD9. In cultured cardiomyocytes, inhibition of BCL10 expression by siRNA prevented palmitate-induced increased p38 MAPK activation and atrial natriuretic peptide (ANP) expression. In contrast, inhibition of p38 MAPK prevented ANP expression, but did not affect BCL10 expression. Deletion of metallothionein abolished the protective effect of zinc on palmitate-induced up-regulation of BCL10 and phospho-p38 MAPK. HFD and zinc deficiency synergistically induce ORCH by increasing oxidative stress-mediated activation of BCL10/CARD9/p38 MAPK signalling. Zinc supplement ameliorates ORCH through activation of metallothionein to repress oxidative stress-activated BCL10 expression and p38 MAPK activation.
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