摘要
Studies have suggested that aluminum, a neurotoxic metal, is involved in the progression of neurodegenerative diseases. Previous studies have confirmed that aluminum influences intracellular Ca^2+ homeostasis. However, it remains unclear whether aluminum increases or decreases intracellular Ca^2+ concentrations. The present study demonstrated that Al^3+ competitively binds to calmodulin (CAM), together with Ca^2+, which resulted in loss of capacity of CaM to bind to Ca^2+, leading to increased [Ca^2+]i. Al^3+ stimulated voltage-gated calcium channels on cell membranes, which allowed a small quantity of Ca^2+ into the cells. Al^3+ also promoted calcium release from organelles by stimulating L-Ca^2+αlc to trigger calcium-induced calcium release. Although Al^3+ upregulated expression of Na+/Ca^2+exchanger mRNA, increased levels of Ca^2+ and Na+/Ca^2+ exchanger did not maintain a normal Ca^2+ balance. Al^3+ resulted in disordered intracellular calcium homeostasis by affecting calcium channels, calcium buffering, and calcium expulsion.
Studies have suggested that aluminum, a neurotoxic metal, is involved in the progression of neurodegenerative diseases. Previous studies have confirmed that aluminum influences intracellular Ca^2+ homeostasis. However, it remains unclear whether aluminum increases or decreases intracellular Ca^2+ concentrations. The present study demonstrated that Al^3+ competitively binds to calmodulin (CAM), together with Ca^2+, which resulted in loss of capacity of CaM to bind to Ca^2+, leading to increased [Ca^2+]i. Al^3+ stimulated voltage-gated calcium channels on cell membranes, which allowed a small quantity of Ca^2+ into the cells. Al^3+ also promoted calcium release from organelles by stimulating L-Ca^2+αlc to trigger calcium-induced calcium release. Although Al^3+ upregulated expression of Na+/Ca^2+exchanger mRNA, increased levels of Ca^2+ and Na+/Ca^2+ exchanger did not maintain a normal Ca^2+ balance. Al^3+ resulted in disordered intracellular calcium homeostasis by affecting calcium channels, calcium buffering, and calcium expulsion.
基金
supported by the Department of Hygienic Toxicology,Public Health College,Harbin Medical University,China