Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P11021 (BiP)
 2,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An elevated blood level of homocysteine is associated with arteriosclerosis and thrombosis. The mechanisms by which homocysteine may promote vascular diseases have not been elucidated yet. In the present study, we have applied a modified nonradioactive differential display analysis to evaluate changes in gene expression induced by homocysteine treatment of cultured human umbilical vein endothelial cells (HUVEC). We identified six up-regulated and one down-regulated genes. One up-regulated gene was GRP78/BiP, a stress protein, suggesting that misfolded proteins would accumulate in the endoplasmic reticulum because of redox potential changes caused by homocysteine. Another up-regulated gene encoded a bifunctional enzyme with activities of methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase, which is involved in a homocysteine metabolism. A third up-regulated gene encoded activating transcription factor 4, and a fourth was a gene whose function is not identified yet. The remaining three were novel genes. We isolated a full-length cDNA of one of the up-regulated genes from a HUVEC library. It encoded a novel protein with 394 amino acids, which was termed reducing agents and tunicamycin-responsive protein (RTP). Northern blot analysis revealed that RTP gene expression was induced in HUVEC after 4 h incubation with homocysteine. RTP mRNA was also observed in unstimulated cells and induced by not only homocysteine but also 2-mercaptoethanol and tunicamycin. The mRNA was ubiquitously expressed in human tissues. These observations indicate that homocysteine can alter the expressivity of multiple genes, including a stress protein and several novel genes. These responses may contribute to atherogenesis.
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PMID:Homocysteine-respondent genes in vascular endothelial cells identified by differential display analysis. GRP78/BiP and novel genes. 893 98

An elevated plasma level of homocysteine is associated with arteriosclerosis and thrombosis. The mechanisms by which homocysteine may promote vascular diseases have not yet been elucidated. In the present study, we have applied a modified nonradioactive differential display analysis to evaluate changes in gene expression induced by homocysteine treatment of cultured human umbilical vein endothelial cells (HUVEC). We identified six upregulated and one downregulated gene. One upregulated gene was GRP78/BiP, a stress protein, suggesting that unfolded proteins would accumulate in the endoplasmic reticulum because of redox potential changes caused by homocysteine. Another upregulated gene encoded a bifunctional enzyme with activities of methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase, which is involved in a homocysteine metabolism. A third upregulated gene encoded activating transcription factor 4. The remaining four were uncharacterized genes. We isolated a full-length cDNA of one of the upregulated genes from a HUVEC library. It encoded a novel protein with 394 amino acids, which was termed reducing-agents and tunicamycin-responsive protein (RTP). Northern blot analysis revealed that RTP gene expression was induced in HUVEC after 4 h of incubation with homocysteine. RTP mRNA was also observed in unstimulated cells and induced by not only homocysteine but also 2-mercaptoethanol and tunicamycin. The mRNA was ubiquitously expressed in human tissues. These observations indicate that homocysteine can alter the expressivity of multiple genes, including a stress protein and several novel genes. These responses may contribute to atherogenesis.
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PMID:Analysis of gene expression in homocysteine-injured vascular endothelial cells: demonstration of GRP78/BiP expression, cloning and characterization of a novel reducing agent-tunicamycin regulated gene. 970 62

Hyperhomocysteinemia is known to be a risk factor for arteriosclerosis and thrombosis. To elucidate the mechanisms by which homocysteine may promote vascular diseases, we have applied a modified nonradioactive differential display analysis that evaluates changes in gene expression induced by homocysteine treatment of cultured human umbilical vein endothelial cells (HUVECs). We identified six upregulated and one downregulated gene. One upregulated gene was GRP78/BiP, an endoplasmic reticulum (ER)-resident molecular chaperone, suggesting that unfolded proteins would accumulate in the ER because of redox potential changes caused by homocysteine. Another upregulated gene encoded a bifunctional enzyme with activities of methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase, which is involved in homocysteine metabolism. A third upregulated gene encoded activating transcription factor 4. Homology searches of the remaining four clones failed to retrieve any similar sequences with a known function. We isolated a full-length cDNA of one of the upregulated genes from a HUVEC library. It encoded a novel protein with 394 amino acids, which was termed RTP (reducing agent and tunicamycin-responsive protein). Northern blot analysis revealed that RTP mRNA expression was induced in HUVECs treated with not only homocysteine but also 2-mercaptoethanol and tunicamycin, both of which are known to induce ER stress. RTP mRNA was ubiquitously expressed in human adult organs, and seemed to be regulated in mouse embryogenesis. Consequently, our differential display analysis revealed that homocysteine alters the expressivity of multiple proteins, especially ER stress-responsive ones. This potential ability of homocysteine may be involved in atherogenesis.
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PMID:Nonradioactive differential display cloning of genes induced by homocysteine in vascular endothelial cells. 1004 51