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Toxicol Mech Methods. 2008 Jan;18(9):751-7. doi: 10.1080/15376510802390908.

Lead-induced stress response in endoplasmic reticulum of astrocytes in CNS.

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Department of Biochemistry and Molecule Biology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning Province, PR China.


Lead is one of the most widespread toxicants in the environment, and its neurotoxicity contributes to a major medical issue. Numerous studies have shown that astrocytes are the main sites of Pb deposition in the central nervous system. A large amount of lead depositing in the astrocyte cells would result in the accumulation of unfolded protein in the endoplasmic reticulum (ER), which up-regulates the expression of molecular chaperones and meanwhile inhibits the cell-cycle progression and the transcription of certain proteins. The unfolded protein response (UPR) could down-regulate the expression of protein cyclinD1 and cause the stagnation of cell-cycle in primary-cultured astrocytes of rat. However, lead neither has obvious effects on the expression of C/EBP homologous protein (CHOP) nor achieves cell apoptosis in the progress of lead-induced UPR. When the stagnation of cell-cycle happens, glucose regulated protein of 78 kDa (GRP78) and other chaperones come to themselves to transport a body of unfolded-protein, consequently making cells survive.


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