University of Louisville
Effects of In Utero Exposure to Arsenic on Expression of Hsp70 in Livers of ApoE-/- Mice at Various Stages of Development
Institution
University of Louisville
Faculty Advisor/ Mentor
J. Christopher States
Abstract
Atherosclerosis, the underlying cause of about 50% of all deaths, is a vascular disease that affects arteries and is characterized by an accumulation of lipids and inflammation. Atherosclerosis often leads to heart attacks and strokes. Exposure to arsenic via drinking water accelerates development of atherosclerosis. However, the mechanisms are unknown. High arsenic exposure causes cellular stress, which induces heat shock protein 70 (Hsp70) expression. We hypothesize that in utero exposure to arsenic in drinking water has long-term effects on expression of Hsp70 in livers of ApoE-/- mice at all stages of development. To test this hypothesis, both control and arsenic-exposed ApoE-/- mice were sacrificed at gestational day 18 (GD18) and 3, 10 and 24 wks. Liver protein extracts were prepared for western blot analysis. Results were quantified and normalized with a loading control (GAPDH). As expected, levels of Hsc70 (constitutive form) were unchanged during the course of development in arsenic exposed mice. Arsenic exposure caused an insignificant increase in levels of Hsp70 (stress-induced form) at GD18. Hsp70 levels increased significantly at 3 weeks and were even greater at 10 weeks in arsenic exposed mice. By 24 weeks, Hsp70 levels return to the levels in unexposed livers. This result supports our hypothesis and shows that arsenic exposure produces a long lasting but not permanent state of stress in livers which can predispose mice to developing atherosclerosis. Supported by NIH Grants # R21ES015812-02S3 (American Reinvestment and Recovery Act Public Service Grant) and P30ES01443.
Effects of In Utero Exposure to Arsenic on Expression of Hsp70 in Livers of ApoE-/- Mice at Various Stages of Development
Atherosclerosis, the underlying cause of about 50% of all deaths, is a vascular disease that affects arteries and is characterized by an accumulation of lipids and inflammation. Atherosclerosis often leads to heart attacks and strokes. Exposure to arsenic via drinking water accelerates development of atherosclerosis. However, the mechanisms are unknown. High arsenic exposure causes cellular stress, which induces heat shock protein 70 (Hsp70) expression. We hypothesize that in utero exposure to arsenic in drinking water has long-term effects on expression of Hsp70 in livers of ApoE-/- mice at all stages of development. To test this hypothesis, both control and arsenic-exposed ApoE-/- mice were sacrificed at gestational day 18 (GD18) and 3, 10 and 24 wks. Liver protein extracts were prepared for western blot analysis. Results were quantified and normalized with a loading control (GAPDH). As expected, levels of Hsc70 (constitutive form) were unchanged during the course of development in arsenic exposed mice. Arsenic exposure caused an insignificant increase in levels of Hsp70 (stress-induced form) at GD18. Hsp70 levels increased significantly at 3 weeks and were even greater at 10 weeks in arsenic exposed mice. By 24 weeks, Hsp70 levels return to the levels in unexposed livers. This result supports our hypothesis and shows that arsenic exposure produces a long lasting but not permanent state of stress in livers which can predispose mice to developing atherosclerosis. Supported by NIH Grants # R21ES015812-02S3 (American Reinvestment and Recovery Act Public Service Grant) and P30ES01443.