Effect Of Lead (Pb) Exposure On The Expression Of Exocrine Peptidase Precursor Gene Ela21in Zebrafish

The environmental impact of lead and industrial lead poisoning are more serious than before with industrial development,. Lead poisoning can cause acute or chronic toxic effects to digestive, nervous, respiratory, and immune system, and usually causes colic, anemia and muscle paralysis and other illnesses. It was reprted that lead poisoning could suppress the activity of aminolevulinate dehydratase (ALAD) in the biosynthesis of heme, resulting in the rise of5-aminolevulinic acid (delta-ALA) in blood and fecal porphyrin in urine, even the coproporphyrinogen content in the urine was significantly higher than normal value.Heme is an essential molecule for numerous living organisms. It’s essential for the transport and storage of oxygen, the generation of cellular energy by respiration, served as a prosthetic group in enzymes (such as:myoglobin, hemoglobin, cytochrome, nitric oxide synthase and peroxide of hydrogen, etc.), and it also acts as a signaling molecule that controls diverse molecular and cellular processes. There are eight enzymes involved in the pathway of heme biosynthesis, which is a very conservative cascade reaction process. Any one of the eight enzyme mutations or defects will result in a specific type of porphyria or anemia.Recentyly papers showed that the defect of heme induced the significantly down-regulation of exocrine peptidase precursor genes transcription in zebrafish, but the mechanism how heme control transcription of exocrine pancreatic zymogen gene is unclear.The LD50of Pb(NO3)2was gotten by the dilution exposure of Pb(NO3)2to zebrafish embryos,It is0.225g/L. Strikingly, after exposured in0.2g/L Pb(NO3)2, the transcription of exocrine peptidase precursor genes ela2l was significantly down-regulated in zebrafish by whole mount in situ hybridization. The down-regulated transcription of ela2l could be restored partily by treatmenmt with hemin, suggesting that lead treatment could imtate the defect of heme in zebrafish. The overexpression vectors of pCS2+-nfe2l2a and pCS2+-hmox-1were constructed for the study on mechanism of the Lead regulation of exocrine peptidase precursor gene expression in zebrafish.It is the first report that Lead can down-regulate the transciption of exocrine peptidase precursor gene ela2l in zebrafish. It is benefit to the study on Lead toxiology, but also to the mechanism how heme control transcription of exocrine pancreatic zymogen gene.