Study on the mechanism underlying Al-induced hepatotoxicity based on the identification of the Al-binding proteins in
Yixin Ding1, Jinlei Tang1, Xun You1
1State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science & Technology, No. 29, 13th Avenue, Tianjin Economy Technological Development Area, Tianjin, 300457, China. dcheng@tust.edu.cn.
Abstract:
Aluminum (Al) is the most abundant metal element in the earth's crust, and is implicated in the pathogenesis of liver lesions. However, the mechanisms underlying Al3+-induced hepatotoxicity are still largely elusive. Based on analysis with native gel electrophoresis, Al3+ plus 8-hydroxyquinoline staining and LC-MS/MS, the proteins with high Al3+ affinity were identified to be carbamoyl-phosphate synthase, adenosylhomocysteinase, heat shock protein 90-alpha, carbonic anhydrase 3, serum albumin and calreticulin. These proteins are involved in physiological processes such as the urea cycle, redox reactions, apoptosis and so on. Then we established an Al3+-treated rat model for biochemical tests, morphology observation and Ca2+ homeostasis analysis, in order to evaluate the extent of oxidative damage, hepatic histopathology and specific indicators of Al3+-related proteins in liver. Our findings indicated the high-affinity interactions with Al3+ perturbed the normal function of the above proteins, which could account for the mechanism underlying Al3+-induced hepatotoxicity.
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