The novel regulations of MEF2A, CAMKK2, CALM3, and TNNI3 in ventricular hypertrophy induced by arsenic exposure in rats

• Published in: Toxicology (Amsterdam) Vol. 324; pp. 123 - 135
• Main Authors: Phan, Nam Nhut, Wang, Chih-Yang, Lin, Yen-Chang
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 03.10.2014
• Subjects: Animals; Apoptosis; Arsenic; Arsenites; Bioinformatics; Blood Pressure; Calcium; Calcium - metabolism; Calcium-Calmodulin-Dependent Protein Kinase Kinase - genetics; Calcium-Calmodulin-Dependent Protein Kinase Kinase - metabolism; Calmodulin - genetics; Calmodulin - metabolism; Cancer; Cardiac function; Computational Biology; Disease Models, Animal; Emergency; Exposure; Gene Expression Regulation; Heart Ventricles - enzymology; Heart Ventricles - pathology; Heart Ventricles - physiopathology; Homeostasis; Hypertension; Hypertrophy, Left Ventricular - chemically induced; Hypertrophy, Left Ventricular - enzymology; Hypertrophy, Left Ventricular - genetics; Hypertrophy, Left Ventricular - pathology; Hypertrophy, Left Ventricular - physiopathology; Male; MEF2 Transcription Factors - genetics; MEF2 Transcription Factors - metabolism; Myocardial Contraction; Pathways; Rats; Rats, Sprague-Dawley; Signal Transduction; Sodium Compounds; Time Factors; Troponin I - genetics; Troponin I - metabolism; Ventricular Function, Left; Ventricular hypertrophy; Ventricular Pressure; Hypertension; Arsenic; Cardiac function; Ventricular hypertrophy
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2014.07.010

Abstract Arsenic is a ubiquitous toxic compound that exists naturally in many sources such as soil, groundwater, and food; in which vast majority forms are arsenite (As3+ ) or arsenate (As5+ ). The mechanism of arsenic detoxification in humans still remains obscured. Epidemiologic studies documented that arsenic pollution caused black foot disease, cardiovascular diseases (hypertension, hypotension, cardiomyopathy), bladder cancer and skin cancer in many countries in which Taiwan is considered as high arsenic exposure country for long time ago. However, the effects of arsenic to cardiac functions still lacked of investigation while some studies mainly focus on inflammatory and cancer mechanisms. In the present study, we found cardiac hypertrophy signaling may be the most significant pathway for up regulated genes in arsenic exposed patients via bioinformatics approach. To verify our bioinformatics prediction, arsenic was fed orally to rats at different concentration based on previous studies in Taiwan. Using hemodynamic method as the main tool to measure the changes in blood pressure, left ventricular pressure and left ventricular contractility index, the findings suggest that highly exposure to arsenic lead to hypertension; elevated left ventricular diastolic pressure and alteration in cardiac contractility which are supposed to be the interaction between arsenic and cardiac nerves activity via the changing in calcium homeostasis. Collectively, based on our real-time PCR and western blot data strongly suggest that calcium homeostasis may also go through MEF2A, TNNI3, CAMKK2, CALM3 and cardiac hypertrophy relative signaling pathway.