Lead-Induced Stress Response in Endoplasmic Reticulum of Astrocytes in CNS

ABSTRACT

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.

KEYWORDS:

• Astrocyte
• Cell-cycle
• Endoplasmic reticulum
• Lead
• Unfolded protein response

The authors’ work is supported by the National Natural Science Foundation China No. 39970651.