Lead affects apoptosis and related gene XIAP and Smac expression in the hippocampus of developing rats.
Lead (Pb) exposure poses devastating effects on central nervous system development of children. To replicate aspects of this neurotoxicity, we examined the effect of lead on the expression of apoptosis and of apoptosis-related genes, XIAP (X chromosome-linked inhibitor of apoptosis protein) and Smac (second mitochondrial activator of caspase), in the hippocampus of developing rats. A total of 48 rats (30-day old) were randomly divided into four groups for intragastrical perfusion of lead acetate [Pb(Ac)2]: untreated, low (2 mg/kg/d), medium (20 mg/kg/d), and high (200 mg/kg/d) dose groups. Pb content was determined in blood, and the apoptosis indexes and XIAP and Smac gene expression were analyzed in the hippocampus. There was a significant difference in apoptosis indexes (AI) between the exposed and control groups (p < 0.01). AI was highest in the high exposure group. XIAP gene expression was reduced in the exposed groups and the expression was negatively correlated with blood lead levels (BLLs) (p < 0.05). But the four groups did not differ in the expression of Smac (p > 0.05). Our data indicate that exposure to Pb(Ac)2 caused a dose-dependent and significant increase of apoptosis in the hippocampus of developing rats through depressing the expression of the XIAP but not the Smac genes.
Liu
Junxiao
J
Analytical Cytology Laboratory and the Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, 22 Xinling Road, 515041 Shantou, Guangdong, People's Republic of China.
Han
Dai
D
Li
Yan
Y
Zheng
Liangkai
L
Gu
Chengwu
C
Piao
Zhongxian
Z
Au
William W
WW
Xu
Xijin
X
Huo
Xia
X
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology*; D020287:In Situ Nick-End Labeling; D020263:Lead Poisoning, Nervous System / Q000235:genetics* / Q000473:pathology*; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics*; D009942:Organometallic Compounds / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics*
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C489013:DIABLO protein, rat; D024101:Mitochondrial Proteins; D009942:Organometallic Compounds; D051636:X-Linked Inhibitor of Apoptosis Protein; D012313:RNA; C008261:lead acetate