Molecular mechanisms regarding potassium bromate‑induced cardiac hypertrophy without apoptosis in H9c2 cells

Abstract

Cardiac hypertrophy is commonly involved in cardiac injury. Oxidative stress can induce cardiac hypertrophy with apoptosis. Potassium bromate (KBrO3) has been widely used as a food additive due to its oxidizing properties. In the present study, the rat‑derived heart cell line H9c2 was used to investigate the effect of KBrO3 on cell size. KBrO3 increased cell size at concentrations <250 µM, in a dose‑dependent manner. Additionally, KBrO3 also promoted the gene expression of two biomarkers of cardiac hypertrophy, brain/B‑type natriuretic peptides (BNP) and β‑Myosin Heavy Chain (β‑MHC). However, apoptosis remained unobserved in these cells. Moreover, mediation of free radicals was investigated using a fluorescence assay, and it was observed that superoxide and reactive oxygen species (ROS) levels increased with KBrO3. Effects of KBrO3 were significantly reduced by tiron at concentrations sufficient to produce antioxidant‑like action. Additionally, signals involved in cardiac hypertrophy such as calcineurin and nuclear factor of activated T‑cells (NFAT) were also determined using western blot analysis. KBrO3 increased the protein levels of both these molecules which were decreased by tiron in a dose‑dependent manner. Additionally, cyclosporine A attenuated the cardiac hypertrophy induced by KBrO3 in H9c2 cells at concentrations effective to inhibit calcineurin, in addition to reducing mRNA levels of BNP or β‑MHC. Finally, apoptosis was also identified in H9c2 cells incubated with KBrO3 at concentrations >300 µM. Collectively, these results provided a novel perspective that KBrO3 induces cardiac hypertrophy without apoptosis at a low dose through the generation of ROS, activating the calcineurin/NFAT signaling pathway in H9c2 cells. Therefore, at a dose <250 µM, KBrO3 can be applied as an inducer of cardiac hypertrophy without apoptosis in H9c2 cells. KBrO3 can also be developed as a tool to induce cardiac hypertrophy in animals.

Cardiac TGR5 expression enhanced by hyperglycaemia in diabetic rats: A preclinical warning for disorders with excess bile acids

“…The protein level of TGR5 and the ratio of p-STAT3 to total STAT3 in the H9c2 cell line were also reduced by stattic in the same manner (Figure 3B). Quantification of the reduction in TGR5 levels (Figure 3C) or the ratio of p-STAT3 to STAT3 (Figure 3D) in the H9c2 cell line supported the dose-dependent effects of stattic, similar to a previous report [26]. These results demonstrated that STAT3 increased TGR5 levels in H9c2 cells under high glucose conditions.…”

Potassium bromate-induced cell model of age-related macular degeneration in vitro

“…KBrO 3 -induced genotoxicity in HepG2 cells indicates that KBrO 3 generates a variety of ROS, resulting in oxidative DNA damage (18). Additionally, KBrO 3 induces an effect in cultured cardiac cells that was similar to the effect mediated by H 2 O 2 (19). Superoxide anion radical generation by KBrO 3 has also been observed (20).…”

“…Cell viability assay. ARPE-19 and 293 cell viability was assessed by performing the MTT assay (19). The purple formazan was dissolved by DMSO.…”

Liraglutide Activates Glucagon-Like Peptide 1 Receptor to Attenuate Hyperglycemia through Endogenous Beta-Endorphin in Diabetic Rats

“…Relative gene expression data were analyzed using real-time quantitative PCR and the 2-∆∆Cq method. This gene expression was shown as the ratio of the target gene level to that of GAPDH, the housekeeping control, as described in our previous report [30]. Each sample was run in duplicate.…”