Telomerase Reverse Transcriptase Regulates Intracellular Ca2+ Homeostasis and Mitochondrial Function via the p53/PGC-1α Pathway in HL-1 Cells

Frontiers in Bioscience-Landmark, Год журнала: 2024, Номер 29(7)

Опубликована: Июль 23, 2024

Background: Telomere shortening is strongly associated with cardiovascular aging and disease, patients shorter telomeres in peripheral blood leukocytes are at higher risk of diseases such as heart failure atrial fibrillation (AF). Telomerase reverse transcriptase (TERT) maintains telomere length, overexpression TERT has been shown to reduce cardiomyocyte apoptosis myocardial infarct size, extend the lifespan aged mice. However, specific impact on electrophysiology cardiomyocytes remains be elucidated. The aims this study were evaluate role Ca2+ homeostasis mitochondrial function myocytes well underlying mechanisms. Methods: overexpressed silenced HL-1 cells constructed lentiviruses, respective empty lentiviral vectors used negative controls. Then patch clamp technique was record electrophysiological characteristics cell action potential duration (APD) L-type currents (ICa,L), flow cytometry detect intracellular concentration membrane (MMP), Seahorse assay measure oxygen consumption rate (OCR). Results: silencing led overload, shortened APD, decreased ICa,L current density, altered gating mechanism, MMP OCR, increased reactive species (ROS), whereas effects. Additionally, resulted overload expression SERCA2a, CaV1.2, NCX1.1, had opposing Furthermore, we discovered that could regulate p53 peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). PGC-1α downregulated by agonist Tenovin-6 but upregulated inhibitor PFTα. effects SR-18292 similar those TERT, ZLN005 produced comparable outcomes overexpression. Conclusions: silencing-induced dysfunction may one mechanism age-related AF. Overexpression reduced basis for arrhythmia formation AF, suggesting a favorable safety profile therapy. regulated through p53/PGC-1α pathway. In addition, might novel target intervention AF should not limited abnormal cation handling.

Язык: Английский

The Effect of Astaxanthin on the Treatment of Neurological Diseases and Lesions

The Neuroscience Journal of Shefaye Khatam, Год журнала: 2024, Номер 13(1), С. 87 - 103

Опубликована: Дек. 1, 2024

Язык: Английский