Disease relevance of HYOU1

• ORP150 protects against hypoxia/ischemia-induced neuronal death [1].
• Oxygen-regulated protein 150 kD (ORP150) is a novel endoplasmic-reticulum-associated chaperone induced by hypoxia/ischemia [1].
• These data indicate that cells of the atherosclerotic vessel wall express ORP150 as part of a protective mechanism, potentially triggered by local hypoxia/hypoxemia and augmented by modified lipoproteins [2].
• In support of a role for ORP150 in the MPs' response to the microenvironment of an atheroma, the presence of oxidized LDL enhanced by approximately 10-fold ORP150 expression in hypoxic cultures [2].
• These results suggest that ORP150 is up-regulated in tumors and, in breast tumors, may be associated with tumor invasiveness [3].

High impact information on HYOU1

• Cultured neurons overexpressing ORP150 were resistant to hypoxemic stress, whereas astrocytes with inhibited ORP150 expression were more vulnerable [1].
• The inducible endoplasmic reticulum chaperone oxygen-regulated protein 150 (ORP150) is expressed in human wounds along with VEGF [4].
• Studies using cultured hippocampal neurons showed that ORP150 regulates cytosolic free calcium and activation of proteolytic pathways causing cell death in neurons subject to excitatory stress [5].
• Expression of the endoplasmic reticulum molecular chaperone (ORP150) rescues hippocampal neurons from glutamate toxicity [5].
• Colocalization of these two molecules was observed in macrophages in the neovasculature, suggesting a role of ORP150 in the promotion of angiogenesis [4].

Chemical compound and disease context of HYOU1

• We have found that exposure of cultured human aortic smooth muscle cells and mononuclear phagocytes (MPs) to hypoxia (pO2 approximately 12-14 torr) induces ORP150 transcripts and production of the antigen, whereas incubation with either hydrogen peroxide, sodium arsenite, heat shock, or 2-deoxyglucose was without effect [2].
• Exposure of MDCK cells to hypoxia resulted in an increase of ORP150 antigen and increased binding of ORP150 to GP80/clusterin (80-kDa glycoprotein), a natural secretory protein in this cell line [6].
• Northern blot analysis revealed that induction of ORP150 in U373 cells was not limited to hypoxia but also observed by 2-deoxyglucose or tunicamycin treatment [7].
• Our data underscore a possible role for ER stress in glutamate toxicity and pinpoint a key ER chaperone, ORP150, which contributes to the stress response critical for neuronal survival [5].
• C6 glioma cells stably transfected with ORP150 antisense displayed selectively reduced ORP150 expression [8].

Biological context of HYOU1

• 150-kDa oxygen-regulated protein (ORP150) suppresses hypoxia-induced apoptotic cell death [9].
• These data indicate that ORP150 has an important cytoprotective role in hypoxia-induced cellular perturbation and that ORP150-associated inhibition of apoptosis may involve mechanisms distinct from those triggered by other apoptotic stimuli [9].
• To assess the participation of the 150-kDa oxygen-regulated protein (ORP150) in protein transport, its function in Madin-Darby canine kidney (MDCK) cells was studied [6].
• Furthermore, the ATP hydrolysis analysis showed that ORP150 can release GP80 at a lower ATP concentration [6].
• We have cloned a cDNA encoding the human 150 kDa oxygen-regulated protein (ORP150) from hypoxia-treated astrocytoma U373 cDNA library [7].

Anatomical context of HYOU1

• Although ORP150 was sparingly upregulated in neurons from human brain undergoing ischemic stress, there was robust induction in astrocytes [1].
• In situ hybridization using ORP150 riboprobes showed the mRNA to be predominantly [correction of predominately] present in macrophages in in atherosclerotic plaques [2].
• To determine the contribution of 150-kDa oxygen-regulated protein (ORP150) to cellular processes underlying adaptation to hypoxia, a cell line stably transfected to overexpress ORP150 antisense RNA was created [9].
• In ORP150 antisense transformant MDCK cells, GP80 was retained within the endoplasmic reticulum after exposure to hypoxia [6].
• These data indicate that ORP150 may function as a unique molecular chaperone in renal epithelial cells by facilitating protein transport/maturation in an environment where less ATP is accessible [6].

Associations of HYOU1 with chemical compounds

• In contrast, diminished levels of ORP150 had no effect on cytotoxicity induced by other stimuli, including oxygen-free radicals and sodium arsenate [9].
• Furthermore, the inhibition of ORP 150 synthesis by transfection of these cells with a specific siRNA resulted in an intensification of apoptosis, as indicated by specific markers of this process; the enhancement of poly ADP-ribose protein cleavage and the increase in Bim protein expression [10].
• Compared with nontransgenic controls, transgenic mice overexpressing ORP150 subjected to renal I/R displayed a blunted rise of serum creatinine and blood urea nitrogen, and enhanced survival of TAL, consistent with cytoprotection [11].
• Using mice heterozygous for ORP150 deficiency, exposure to excitatory stimuli caused hippocampal neurons to display exaggerated elevation of cytosolic calcium accompanied by activation of mu-calpain and cathepsin B, as well as increased vulnerability to glutamate-induced cell death in vitro and decreased survival to kainate in vivo [5].
• We show that an inducible chaperone present in endoplasmic reticulum (ER), the 150-kDa oxygen-regulated protein (ORP150), is expressed both in the human brain after seizure attack and in mouse hippocampus after kainate administration [5].
• Our observations led to the hypothesis that ORP150 protects against MPTP/MPP(+)-induced neurotoxicity, and indicate the importance of the ER environment in maintaining the nigrostriatal pathways [12].

Regulatory relationships of HYOU1

• Different inflammatory cytokines did not modify expression, whereas IFN-gamma down-regulated and hypoxia up-regulated CXCR4 transcripts [13].
• Hypoxia up-regulated angiogenin and down-regulated vascular cell adhesion molecule-1 expression and secretion in human placental trophoblasts [14].

Other interactions of HYOU1

• The N-terminal half of ORP150 exhibits significant similarity to the ATPase domain of HSP70 family proteins with well-conserved ATP binding motifs [7].
• Furthermore, tissue specificity of expression of ORP150 was quite similar to that of GRP78 [7].
• Western and Northern blotting demonstrated elevated expression of ORP150 in breast cancer, regardless of estrogen receptor status, compared with normal breast tissue [3].
• The trend was the same for the staining score of MMP-2, and there was a significant correlation between ORP150 and MMP-2 expression [15].
• Expression of the oxygen-regulated protein ORP150 accelerates wound healing by modulating intracellular VEGF transport [4].

Analytical, diagnostic and therapeutic context of HYOU1

• The increased expression of ORP150 and GRP78 in IRPTCs with albumin overload was detected by Western blot and immunofluorescence study [16].
• The 150 kDa oxygen-regulated protein (ORP150) is an inducible endoplasmic reticulum (ER) chaperone with cytoprotective properties in settings of cell stress, such as ischemia/reperfusion (I/R) [11].
• The hypoxia up-regulated genes identified could be important for the survival and functioning of macrophages in hypoxic diseased tissues, and their promoters could prove useful in macrophage-delivered gene therapy [17].

References