title: Effects of lanthanum chloride on glutamate level, intracellular calcium concentration and caspases expression in the rat hippocampus.
abstract: Lanthanum chloride (LaCl(3)) can affect neurobehavioral development and impair cognitive abilities. The mechanism underlying LaCl(3)-induced neurotoxic effects is still unknown. The purpose of this research was to investigate the neuronal impairment induced by LaCl(3) and discuss the possible mechanism from the aspects of the alteration of glutamate level, intracellular calcium concentration ([Ca(2+)](i)), Bax, Bcl-2 and caspases expression in the hippocampus. Lactational rats were exposed to 0, 0.25, 0.50 and 1.0 % LaCl(3) in drinking water, respectively. Their offspring were exposed to LaCl(3) by parental lactation and then administrated with 0, 0.25, 0.50 and 1.0 % LaCl(3) in drinking water for 1 month. The results showed that 0.25, 0.50 and 1.0 % LaCl(3) exposure induced neuronal impairment in the hippocampus of young rat. Hippocampal glutamate level, [Ca(2+)](i) and ratio of Bax and Bcl-2 expression increased significantly after LaCl(3) exposure. Besides, LaCl(3) exposure increased GRP78, GRP94, GADD153 and p-JNK expression, promoted the activation of caspase-3, caspase-9 and caspase-12, induced PARP cleavage and caused excessive apoptosis. These results indicate that LaCl(3) increases glutamate level, [Ca(2+)](i) and ratio of Bax and Bcl-2 expression, which cause excessive apoptosis by the mitochondrial and endoplasmic reticulum stress-induced pathway, and thus neuronal damages in the hippocampus.
authors.affiliation: Department of Toxicology, School of Public Health, China Medical University, 92 North 2nd Road, Shenyang, 110001, PR China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yang
authors.forename: Qiufang
authors.initials: Q
authors.lastname: Liu
authors.forename: Shengwen
authors.initials: S
authors.lastname: Wu
authors.forename: Qi
authors.initials: Q
authors.lastname: Xi
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007811:Lanthanum / Q000633:toxicity*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009562:Nissl Bodies / Q000187:drug effects / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051742:Transcription Factor CHOP / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D002118:Calcium; D020169:Caspases; D004785:Environmental Pollutants; D018698:Glutamic Acid; D006360:Heat-Shock Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D007811:Lanthanum; D008562:Membrane Glycoproteins; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D019253:Proto-Oncogene Proteins c-bcl-2; D051742:Transcription Factor CHOP; D051028:bcl-2-Associated X Protein; C494828:Bax protein, rat; C497251:Ddit3 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C053387:endoplasmin; C028521:lanthanum chloride; C499322:Parp1 protein, rat