title: The novel regulations of MEF2A, CAMKK2, CALM3, and TNNI3 in ventricular hypertrophy induced by arsenic exposure in rats.
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 (As(3+)) or arsenate (As(5+)). 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.
authors.affiliation: Graduate Institute of Biotechnology, Chinese Culture University, 55 Hwa-Kang Road, Yang-Ming-Shan, Taipei 11114, Taiwan.
authors.forename: Nam Nhut
authors.initials: NN
authors.lastname: Phan
authors.affiliation: Department of Anatomy, University of California, San Francisco, CA, USA; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Graduate Institute of Biotechnology, Chinese Culture University, 55 Hwa-Kang Road, Yang-Ming-Shan, Taipei 11114, Taiwan. Electronic address: lycnthu@gmail.com.
authors.forename: Yen-Chang
authors.initials: YC
authors.lastname: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis; D018053:Arsenites; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000235:genetics / Q000378:metabolism*; D002147:Calmodulin / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D064326:MEF2 Transcription Factors / Q000235:genetics / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D017670:Sodium Compounds; D013997:Time Factors; D019210:Troponin I / Q000235:genetics / Q000378:metabolism*; D016277:Ventricular Function, Left; D017725:Ventricular Pressure
chemical_list: D018053:Arsenites; D002147:Calmodulin; D064326:MEF2 Transcription Factors; C578037:MEF2A protein, rat; D017670:Sodium Compounds; D019210:Troponin I; C017947:sodium arsenite; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; C517702:Camkk2 protein, rat; D002118:Calcium
keywords: Arsenic; Cardiac function; Hypertension; Ventricular hypertrophy