150-kD oxygen-regulated protein is expressed in human atherosclerotic plaques and allows mononuclear phagocytes to withstand cellular stress on exposure to hypoxia and modified low density lipoprotein.

Abstract

The 150-kD oxygen-regulated protein (ORP150) was initially characterized based on its selective expression in astrocytes subjected to oxygen deprivation (Kuwabara, K., M.

150-kDa Oxygen-regulated Protein (ORP150) Suppresses Hypoxia-induced Apoptotic Cell Death

“…Expression of ORP150, a stress protein originally purified and cloned from cultured rat astrocytes subjected to hypoxia, has been observed in several types of cells subjected to oxygen deprivation (9,10,13). Factors responsible for ORP150 expression are also present in atherosclerotic lesions and in breast cancers.…”

“…Expression of ORP150 mRNA in HEK cells exposed to hypoxia employed a partial ORP150 cDNA corresponding to 151-570 base pairs (amino acids 51-190) for Northern analysis, as described (13). About 20 g of total RNA was extracted from HEK cells exposed to hypoxia or normoxia for the indicated times by the AGPC method; RNA was separated by electrophoresis on 1.0% agarose/formamide gels and transferred overnight onto Biodyne B paper (Pall BioSupport, New York).…”

“…Because of the striking induction of ORP150 expression in cultured astrocytes (10) and mononuclear phagocytes (13) exposed to hypoxia, we speculated that this protein might have a cytoprotective role in response to cell stress associated with oxygen deprivation. To address this issue, we have established a cell line stably transfected to overexpress ORP150 antisense RNA in human embryonic kidney (HEK) cells.…”

Induction of heme oxygenase-1 inhibits the monocyte transmigration induced by mildly oxidized LDL.

“…In contrast, the mechanisms of endogenous prevention of LDL oxidation other than those related to HDL, or exogenous antioxidants like probucol (36) or ␣ -tocopherol (37) are not generally well understood. It was recently reported using in vitro studies that oxidized LDL triggers expression of HO-1, heat shock protein 70 (HSP 70), macrophage stress protein 23 (MSP23), and a 150-kD oxygen-regulated protein (ORP150) as stress proteins in vascular endothelial cells, vascular smooth muscle cells, macrophages, and renal tubular epithelial cells (38)(39)(40)(41). However, the functions of these stress proteins are unknown.…”

Targeting of the molecular chaperone oxygen-regulated protein 150 (ORP150) to mitochondria and its induction by cellular stress

“…Upregulation of ORP150 has been observed after hypoxia, serum starvation, ischemia, in cancer, and after treatment with tunicamycin or 2-deoxyglucose (1, 5, 6, 12-14, 21-23, 27, 32). The functions of ORP150 have not been fully elucidated, but it appears to play a role in apoptosis (1, 6, 12-14, 21, 23, 24, 27, 30), insulin secretion (15,16), protein transport (26), and wound healing (26,31). Much of what is known about ORP150 arises from studies utilizing antisense, adenovirus-mediated, or whole animal knockdown of protein expression (1,6,14).…”