Challenging the Metallothionein (MT) Gene of Biomphalaria glabrata: Unexpected Response Patterns Due to Cadmium Exposure and Temperature Stress

Metallothioneins (MT) are low-molecular-weight, cysteine-rich, metal-binding proteins. MT genes are readily induced by various physiologic and toxicologic stimuli. Because the cysteines in MT are absolutely conserved across species, it was suspected that the cysteines are necessary for function and MT is essential for life. In attempts to determine the function(s) of MT, studies have been performed using four different experimental paradigms: (a) animals injected with chemicals known to induce MT; (b) cells adapted to survive and grow in high concentrations of MT-inducing toxicants; (c) cells transfected with the MT gene; and (d) MT-transgenic and MT-null mice. Most often, results from studies using the first three approaches have indicated multiple functions of MT in cell biology: MT (a) is a "storehouse" for zinc, (b) is a free-radical scavenger, and (c) protects against cadmium (Cd) toxicity. However, studies using MT-transgenic and null mice have not strongly supported the first two proposed functions but strongly support its function in protecting against Cd toxicity. Repeated administration of Cd to MT-null mice results in nephrotoxicity at one tenth the dose that produces nephrotoxicity in control mice. Human studies indicate that 7% of the general population have renal dysfunction from Cd exposure. Therefore, if humans did not have MT, "normal" Cd exposure would be nephrotoxic to humans. Thus, it appears that during evolution, the ability of MT to protect against Cd toxicity might have taken a more pivotal role in the maintenance of life processes, as compared with its other proposed functions (i.e. storehouse for zinc and free radical scavenger).

The first comprehensive study on the global burden of disease and risk factors was commissioned by the World Bank in 1992. A follow-up study was performed in 2005, and another iteration was commissioned by the World Health Organization in 2010, due for publication in 2011. The author suggests that the global burden of neglected tropical diseases (NTDs) has been seriously underestimated. The way forward is the integration of control efforts, with programmes coming together to deliver a package of drugs against NTDs. Barriers to continent-wide coverage of drugs against NTDs are political will (missing in those countries with poor governance), funding (approximately half of the $1.5-2 billion is needed) and human resources. However, if the donors who give so much to malaria, tuberculosis and human immunodeficiency virus would share just 10% of the amount allocated to the big three, the most common NTDs could become diseases of the past. This could well happen within 7 years, and the targets of GET2020 (Global Elimination of Trachoma by 2020) to eliminate trachoma and GAELF (the Global Alliance to Eliminate Lymphatic Filariasis) to eliminate lymphatic filariasis by 2020 are achievable. Copyright © 2011 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.