Open AccessP‐cresyl sulfate causes mitochondrial hyperfusion in H9C2 cardiomyoblasts
Author(s) -
Huang TienHung,
Yip HonKan,
Sun CheukKwan,
Chen YiLing,
Yang ChihChao,
Lee FanYen
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15303
Subject(s) - mitochondrial biogenesis , tfam , mitochondrion , ampk , mitochondrial dna , microbiology and biotechnology , adenosine triphosphate , mitochondrial fusion , chemistry , membrane potential , adenosine monophosphate , biology , protein kinase a , adenosine , phosphorylation , biochemistry , gene
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.