P‐cresyl sulfate causes mitochondrial hyperfusion in H9C2 cardiomyoblasts

• Published in: Journal of cellular and molecular medicine Vol. 24; no. 15; pp. 8379 - 8390
• Main Authors: Huang, Tien‐Hung, Yip, Hon‐Kan, Sun, Cheuk‐Kwan, Chen, Yi‐Ling, Yang, Chih‐Chao, Lee, Fan‐Yen
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.08.2020; John Wiley and Sons Inc
• Subjects: Adenosine kinase; AMP; AMP-Activated Protein Kinases - metabolism; Animals; Antibodies; Apoptosis; Apoptosis - drug effects; Cell growth; Cell Line; Cell proliferation; Cell Proliferation - drug effects; Cell size; Copy number; Cresols - pharmacology; Cytology; Deoxyribonucleic acid; DNA; Kidney diseases; Membrane potential; Membrane Potential, Mitochondrial - drug effects; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondrial DNA; Morphology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Original; Oxygen consumption; Oxygen Consumption - drug effects; Phosphorylation; Protein kinase; p‐cresyl sulphate; Rats; Respiration; Software; stress‐induced mitochondrial hyperfusion; Sulfates; Sulfuric Acid Esters - pharmacology; p-cresyl sulphate; stress-induced mitochondrial hyperfusion; mitochondria
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.15303

Increased circulating level of uraemic solute p‐cresyl sulphate (PCS) in patients with chronic kidney disease (CKD) is known to increase myocardial burden relevant to mitochondrial abnormalities. This study aimed at investigating mitochondrial response to PCS in H9C2 cardiomyoblasts. H9C2 cardiomyoblasts were treated with four different concentrations of PCS (3.125, 6.25, 12.5 and 25.0 µg/mL) to study the changes in cell proliferation, cell size and mitochondrial parameters including morphology, respiration, biogenesis and membrane potential. The lowest effective dose of PCS (6.25 µg/mL) induced mitochondrial hyperfusion with enhanced mitochondrial connectivity, mitochondrial oxygen consumption rates, mitochondrial mass, mitochondrial DNA copy number and increased volume of cardiomyoblasts. After PCS treatment, phosphorylation of energy‐sensing adenosine monophosphate‐activated protein kinase (AMPK) was increased without induction of apoptosis. In contrast, mitochondrial mass was recovered after AMPK silencing. Additionally, mitochondrial hyperfusion and cell volume were reversed after cessation of PCS treatment. The results of the present study showed that low‐level PCS not only caused AMPK‐dependent mitochondrial hyperfusion but also induced cell enlargement in H9C2 cardiomyoblasts in vitro.