Gene Expression Profiles of Cultured Rat Cardiomyocytes (H9C2 Cells) in Response to Arsenic Trioxide at Subcytotoxic Level and Oxidative Stress

Abstract

Epidemiologic studies have suggested a close correlation between arsenic exposure and cardiovascular disease. In mechanism studies of heart disease and arsenic exposure, blood vessels, vascular smooth muscle cells, and endothelial cells of the artery have long been thought to be the primary targets in arsenic exposure but there are only a few studies on cardiomyocytes. In this study, to predict more diverse responses of cardiomyocytes to arsenic exposure in the development of heart failure, gene expression profiles of cultured rat cardiomyocytes (H 9 C 2 cell line) were evaluated using the rat whole-genome microarray when a subcytotoxic level of arsenic trioxide was treated. After 24 hr of arsenic 0.5 ppm exposure (As 2 O 3 was used), 405 genes were up-regulated including heme oxygenase-1, and 499 genes were down-regulated including fibroblast growth factor. With the subcytotoxic dose of As 2 O 3 , oxidative stress was generated without cell death, and the transcription of stress-related genes such as heme oxygenase-1, glutathione S-transferase, metallothionein, and catalase were significantly increased. Direct measurement of reactive oxygen species using fluorescent dye showed that arsenic caused oxidative stress at the subcytotoxic level. Although no direct comparison was made among different types of cells in this study, it appears that arsenic can cause physiologic adverse reactions at a relatively low level in cardiomyocytes and that cardiomyocytes are also one of the vulnerable targets of heart failure by arsenic compounds.

Prophylactic effect of coconut water (Cocos nucifera L.) on ethylene glycol induced nephrocalcinosis in male wistar rat

“…The amplification of different antioxidant enzymes was carried out by using specific primers viz, SOD (forward primer 5'-GCA GAA GGC AAG CGG TGA AC-3', reverse primer 5'-TAG CAG GAC AGC AGA TGA GT-3', 446 bp), catalase (forward primer 5'-GCG AAT GGA GAG GCA GTG TAC-3', reverse primer 5'-GAG TGA CGT TGT CTT CAT TAG CAC TG-3', 652 bp). GA-PDH was chosen as house keeping gene (forward primer 5'-TCT AAG AAA CAT GGC GGT CC-3' reverse primer 5'-CAG TTA GCA GGC CAG CAG AT-3', 197bp) (16)(17)(18)(19)(20). PCR products were resolved on 1% agarose gels.…”

Arsenic and the Cardiovascular System

“…Using whole-genome microarray, Park and Park showed that just 24 hours following ATO treatment, H9c2 cardiomyocytes up-regulated 405 genes and down-regulated 499 genes by more than two-fold indicating the large physiological changes As exposure can induce in a relatively short period of time [119]. In this study, ATO treatment at a subcytotoxic dose (0.5 ppm) increased ROS generation, which led to oxidative stress as indicated by up-regulation of HO-1, GST, metallothionein (MT), and catalase.…”

“…In this study, ATO treatment at a subcytotoxic dose (0.5 ppm) increased ROS generation, which led to oxidative stress as indicated by up-regulation of HO-1, GST, metallothionein (MT), and catalase. Despite ROS generation and oxidative stress, As exposure also induces cardiotoxicity by modulating ion channels [119]. Metallothionein is a well-known endogenous antioxidant that plays a vital role in regulating heavy metals in biological systems [4].…”

Sodium Arsenite-Induced Alteration in Hepatocyte Function of Rat with Special Emphasis on Superoxide Dismutase Expression Pathway and its Prevention by Mushroom Lectin

“…Cell viability was measured through MTT assay [10]. The cells were seeded on 24-well tissue culture plates with 2 · 10 5 cells per well, and the medium was changed 24 hr.…”