THE ARSENIC-IRON REDOX REACTION IN THE PATHWAY TO REACTIVE OXYGEN SPECIES

picture of Jinglu Shi presenting his/her poster: THE ARSENIC-IRON REDOX REACTION IN THE PATHWAY TO REACTIVE OXYGEN SPECIES

Jinglu Shi , Timothy R. Radabaugh, Terrence J. Monks, Serrine S. Lau

THE ARSENIC-IRON REDOX REACTION IN THE PATHWAY TO REACTIVE OXYGEN SPECIES

The worldwide phenomenon of arsenic poisoning is being investigated extensively due to its hazardous health effects. Arsenic is a metalloid that is found naturally in water, soil, air, and wild life, and can have long-term health effects such as cancer and cardiovascular disease. The EPA reports a standard of arsenic in drinking water of 10-50 ppb. An increase in reactive oxygen species (ROS) associated with arsenic exposure has already been shown in human bladder cells (Eblin, 2008). ROS are a normal byproduct of oxygen metabolism, but can cause oxidative damage in cells when ROS levels are exacerbated. MTS assays have also shown that arsenite caused decreases in macrophage viability in as little as 12 hours, and most cells showed little viability within 48 hours. The mechanism by which arsenic induces oxidative damage, however, is still unknown. A possible speculation is through the release of iron from ferritin. Ferritin is a protein that stores iron in its Fe(III) form and releases it as Fe(II). Free iron can be toxic because of its involvement in the Fenton reaction to produce free radicals, ergo inducing oxidative damage. The following redox reaction, Fe(III) + As(III) à As(V) + Fe(II), in which arsenite is reducing stored Fe(III) in ferritin to cause release of free iron, may be the pathway responsible for the oxidative damage seen. Iron uptake levels were assayed on apoferritin proteins exposed to both 100uM phosphate and arsenite. Both the oxyanions showed decreased iron uptake in ferritin compared to ferritin without either toxicants. Iron release assays (Boyer, 1987) were also conducted and ferritin that contained the oxyanions released more iron than ferritin that didn’t contain either toxicant. Elevated levels of phosphate or arsenite may be inducing the formation of oxyanion clusters around the stored iron within the ferritin molecule, leading to a decrease in iron uptake and an increase in iron release. These results have yet to be confirmed in cells. Because of the ubiquity of the ferritin protein in living organisms, this pathway could help explain the causes of some of the long-term health effects that arsenic is responsible for. (P30ES006694)

 

 

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