Influence of arsenate and arsenite on signal transduction pathways: an update

Abstract

Arsenic has been a recognized contaminant and toxicant, as well as a medicinal compound throughout human history. Populations throughout the world are exposed to arsenic and these exposures have been associated with a number of human cancers. Not much is known about the role of arsenic as a human carcinogen and more recently its role in non-cancerous diseases, such as cardiovascular disease, hypertension and diabetes mellitus have been uncovered. The health effects associated with arsenic are numerous and the association between arsenic exposure and human disease has intensified the search for molecular mechanisms that describe the biological activity of arsenic in humans and leads to the aforementioned disease states. Arsenic poses a human health risk due in part to the regulation of cellular signal transduction pathways and over the last few decades, some cellular mechanisms that account for arsenic toxicity, as well as, signal transduction pathways have been discovered. However, given the ubiquitous nature of arsenic in the environment, making sense of all the data remains a challenge. This review will focus on our knowledge of signal transduction pathways that are regulated by arsenic.

Dietary methyl-consuming compounds and metabolic syndrome

“…Chronic exposure to arsenic has been recognized to cause various types of human diseases, including metabolic syndrome, T2D, CVD and various cancers, [40][41][42][43][44] which may contribute to the prevalence of metabolic syndrome in arsenic-polluted areas. The mechanism underlying arsenic toxicity is believed to be due to methyl depletion-induced aberrant DNA methylation, and excessive ROS generation and subsequent oxidative cell injury.…”

“…The mechanism underlying arsenic toxicity is believed to be due to methyl depletion-induced aberrant DNA methylation, and excessive ROS generation and subsequent oxidative cell injury. [40][41][42]45 Niacin Niacin (nicotinic acid and nicotinamide) is a water-soluble vitamin and a common methyl consumer. 46 Dietary nicotinic acid is derived from plant foods, while nicotinamide is derived from animal foods and typically used for food fortification.…”

Molecular analysis, developmental function and heavy metal-induced expression of ABCC5 in zebrafish

“…These nonessential metals gain entry into cells by simple diffusion or through membrane carriers and ion channels (Blazka and Shaikh, 1992;Souza et al, 1997;Bridges and Zalups, 2005). Upon entering cells, heavy metals exert multiple adverse effects through interfering with functions of essential metals, generating reactive oxygen species (ROS) (Ercal et al, Comparative Biochemistry and Physiology, Part B 158 (2011) [46][47][48][49][50][51][52][53][54][55] 2001; Ahamed and Siddiqui, 2007), disrupting physiological signal transduction (Thevenod, 2009;Druwe and Vaillancourt, 2010), affecting gene expression (Gonzalez et al, 2010), inducing damages to DNA, membranes and proteins, and inhibiting DNA repair (Bertin and Averbeck, 2006). At the tissue level, exposure to heavy metals results in developmental defects, generation of tumors and adverse effects on a number of human organs including kidney, liver, lung, pancreas, testis, and placenta (Zalups and Ahmad, 2003).…”

MRP proteins as potential mediators of heavy metal resistance in zebrafish cells

“…These nonessential metals gain entry into cells through simple diffusion, membrane carriers or ion channels (Blazka and Shaikh, 1992;Bridges and Zalups, 2005;Souza et al, 1997). Upon entering cells, heavy metals exert multiple adverse effects through interfering with the functions of essential metals, generating reactive oxygen species (ROS) (Ahamed and Siddiqui, 2007;Ercal et al, 2001), disrupting physiological signal transduction (Druwe and Vaillancourt, 2010;Thevenod, 2009), affecting gene expression (Gonzalez et al, 2010), inducing damages to DNA, membranes and proteins, and inhibiting DNA repair (Bertin and Averbeck, 2006). At the tissue level, exposure to heavy metals results in developmental defects, generation of tumors and adverse effects on a number of human organs including kidney, liver, lung, pancreas, testis, and placenta (Zalups and Ahmad, 2003).…”