PDCD5 (programmed cell death 5) is ubiquitously expressed in tissues, including the heart; however, the mechanism underlying the cardiac function of PDCD5 has not been understood. We investigated the mechanisms of PDCD5 in the pathogenesis of cardiac hypertrophy. Cardiac-specific PDCD5 knockout mice developed severe cardiac hypertrophy and impaired cardiac function, whereas PDCD5 protein was significantly increased in transverse aortic constriction mouse hearts and phenylephrine-stimulated cardiomyocytes. Overexpression of PDCD5 inhibited phenylephrine-induced cardiomyocyte hypertrophy, and knockdown of PDCD5 induced cardiomyocyte hypertrophy and aggravated phenylephrine-induced hypertrophy. The expression of PDCD5 protein was regulated by NFATc2 (nuclear factor of activated T cells c2) during hypertrophy. SERCA2a (sarco/endoplasmic reticulum Ca-ATPase 2a) expression was decreased in PDCD5-deficient mouse hearts because of increased ubiquitination. PDCD5-deficient cardiomyocytes displayed decreased calcium uptake rate, slowed decay of Ca transients, decreased calcium stores, and diastolic dysfunction. Moreover, reintroduction of PDCD5 in PDCD5-deficient mouse hearts reserved SERCA2a protein, suppressed NFATc2 protein, and rescued the hypertrophy and cardiac dysfunction. Our results revealed that PDCD5 is a novel target of NFATc2 in the hypertrophic heart and provides negative feedback to protect the heart against excessive hypertrophy via the stabilization of SERCA2a protein.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1161/HYPERTENSIONAHA.118.11357 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
TRADD-mediated pyroptosis contributes to diabetic cardiomyopathy.
Acta Pharmacol Sin
January 2025
Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, 226001, China.
Regulated cell death like pyroptosis is one vital cause of diabetic cardiomyopathy (DCM), which eventually leads to heart failure. Tumor necrosis factor (TNF) receptor-associated death domain protein (TRADD) is an adapter protein with multiple functions that participates in the pathophysiological progress of different cardiovascular disorders via regulating regulated cell death. Studies have shown that TRADD combines with receptor-interacting protein kinase 3 (RIPK3) and facilitates its activation, thereby mediating TNF-induced necroptosis.
View Article and Find Full Text PDFSNX3 mediates heart failure by interacting with HMGB1 and subsequently facilitating its nuclear-cytoplasmic translocation.
Acta Pharmacol Sin
January 2025
National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Guangdong Province Engineering Laboratory for Druggability and New Drug Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
Sorting nexins (SNXs) as the key regulators of sorting cargo proteins are involved in diverse diseases. SNXs can form the specific reverse vesicle transport complex (SNXs-retromer) with vacuolar protein sortings (VPSs) to sort and modulate recovery and degradation of cargo proteins. Our previous study has shown that SNX3-retromer promotes both STAT3 activation and nuclear translocation in cardiomyocytes, suggesting that SNX3 might be a critical regulator in the heart.
View Article and Find Full Text PDFCardiac pathology associated with hypertension and chronic kidney disease in aged cats.
J Comp Pathol
January 2025
Department of Comparative Biomedical Sciences, Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK. Electronic address:
Hypertension is a common condition in older cats, often secondary to chronic kidney disease (CKD). Although the heart is one of the organs damaged by hypertension, the pathology of the feline hypertensive (HT) heart has been poorly studied. The aim of this retrospective study was to describe the gross and microscopic pathology of hearts obtained from cats at post-mortem examination and to compare cats diagnosed with hypertension with cats of similar age and kidney function for which antihypertensive treatment was not deemed clinically necessary.
View Article and Find Full Text PDFPrognostic Implications of Cardiac Geometry in Cirrhosis: Findings From a Large Cohort.
Liver Int
February 2025
General Practice Ward/International Medical Center Ward, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, China.
Background And Aims: Cirrhosis is characterised by hyperdynamic circulation, which contributes to cirrhotic cardiomyopathy (CCM). However, the expert consensus on CCM did not initially include cardiac structure because of scant evidence. Therefore, this study investigated the associations of cardiac chamber geometry with mortality and CCM.
View Article and Find Full Text PDFDl-3-n-butylphthalide Alleviates Cardiac Dysfunction and Injury Possibly by Inhibiting Cell Pyroptosis and Inflammation via the cGAS-STING-TBK1 Pathway in a Porcine Model of Hemorrhage-Induced Cardiac Arrest.
Shock
December 2024
Department of Emergency Medicine, Ningbo Medical Center Lihuili Hospital, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, China.
Introduction: Dl-3-n-butylphthalide (NBP), a small molecular compound extracted from celery seeds, has been shown to exhibit diverse pharmacological activities, including anti-inflammatory, antioxidative, and anti-apoptotic effects. Recent studies have highlighted its efficacy in treating various cardiovascular conditions, such as myocardial infarction, hypertrophy, heart failure, and cardiotoxicity. This study aimed to investigate whether NBP could alleviate cardiac dysfunction and injury following hemorrhage-induced cardiac arrest (HCA) in a porcine model and elucidate its potential mechanisms.
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!