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)

Respiratory syncytial virus (RSV) infection induced programmed cell death or apoptosis in the cultured lung epithelial cell line, A549. The apoptotic cells underwent multiple changes, including fragmentation and degradation of genomic DNA, consistent with the activation of the DNA fragmentation factor or caspase-activated DNase (DFF or CAD). The infection led to activation of FasL; however, a transdominant mutant of FAS-downstream death domain protein, FADD, did not inhibit apoptosis. Similarly, modest activation of cytoplasmic apoptotic caspases, caspase-3 and -8, were observed; however, only a specific inhibitor of caspases-3 inhibited apoptosis, while an inhibitor of caspase-8 had little effect. No activation of caspase-9 and -10, indicators of the mitochondrial apoptotic pathway, was observed. In contrast, RSV infection strongly activated caspase-12, an endoplasmic reticulum (ER) stress response caspase. Activation of the ER stress response was further evidenced by upregulation of ER chaperones BiP and calnexin. Antisense-mediated inhibition of caspase-12 inhibited apoptosis. Inhibitors of NF-kappa B had no effect on apoptosis. Thus, RSV-induced apoptosis appears to occur through an ER stress response that activates caspase-12, and is uncoupled from NF-kappa B activation.
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PMID:An endoplasmic reticulum-specific stress-activated caspase (caspase-12) is implicated in the apoptosis of A549 epithelial cells by respiratory syncytial virus. 1113 74

Endoplasmic reticulum (ER) stress is involved in the pathophysiology of atherosclerosis. Insults interfering with ER function lead to the accumulation of unfolded and misfolded proteins in the ER that initiates the unfolded protein response (UPR). When the UPR fails to control the level of unfolded and misfolded proteins, ER-initiated apoptotic signaling is induced. We evaluated: (1) the UPR and ER-initiated apoptotic signaling in peripheral blood mononuclear cells (PBMCs) of stable coronary artery disease (CAD) patients; (2) PBMC content of oxidation products of phospholipid 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (oxPAPC); (3) the possible origin of oxPAPC in PBMCs; and (4) the expression of nuclear erythroid-related factor 2 (Nrf2)/antioxidant-related element (ARE), a cellular defense mechanism. Twenty-nine CAD patients and 28 matched controls were enrolled. Expression of glucose-regulated protein 78kDa (GRP78/BiP), as a representative of the UPR, and of C/EBP homologous protein (CHOP), as a representative of ER apoptosis, was significantly higher in CAD than in controls (p<0.01). Concentrations of oxPAPC in PBMCs, in plasma, and in low-density lipoprotein (LDL) were significantly higher in CAD compared to controls (p<0.01). The oxPAPC in PBMCs may derive from circulating ox-LDL. Nrf2/ARE gene expression and circulating and cellular glutathione were significantly lower in CAD compared to controls (p<0.01). In in vitro studies, increasing amounts of oxPAPC induced a dose-dependent increase in CHOP and apoptosis-related protein expression (p<0.01) and a progressive decrease in Nrf2/ARE gene expression (p<0.01). In PBMCs of CAD patients there is an activation of the UPR and ER-initiated apoptotic signaling, possibly related to an abnormal concentration of oxPAPC in PBMCs.
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PMID:Increased endoplasmic reticulum stress and Nrf2 repression in peripheral blood mononuclear cells of patients with stable coronary artery disease. 2437 61