The low density lipoprotein receptor (LDLR)-related protein (LRP) is a multifunctional receptor which mediates the endocytic uptake of several ligands implicated in Alzheimer's disease pathophysiology. Although LRP, as a member of the LDLR family, is likely to be regulated in response to various cellular stresses, this regulation has not been fully understood yet. In the present study we studied the regulation of LRP expression in primary cultured rat astrocytes in response to serum deprivation as a general cellular stress. A significant increase in LRP expression was detected after serum deprivation and this increase was blocked by treatment of U0126, an inhibitor of MAP kinase. This serum deprivation action was Partially reversed by either serum or D-glucose supplementation, but further augmented by glutamine. This result contrasted with a finding that glutamine suppressed gadd153 protein induced by serum deprivation. Taken together, the present data suggest that serum deprivation induces dramatically LRP expression in astrocytes partly by MAPK signaling pathways and by signaling pathways apparently distinct from gadd153 induction. (C) 2002 Elsevier Science (USA). All rights reserved.