Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transcription factor BTB and CNC homology 1 (Bach1) regulates genes involved in the oxidative stress response and cell-cycle progression. We have recently shown that Bach1 impairs cell proliferation and promotes apoptosis in cultured endothelial cells (ECs), but the underlying mechanisms are largely uncharacterized. Here we demonstrate that Bach1 upregulation impaired the blood flow recovery from hindlimb ischemia and this effect was accompanied both by increases in reactive oxygen species (ROS) and cleaved caspase 3 levels and by declines in the expression of cyclin D1 in the injured tissues. We found that Bach1 overexpression induced mitochondrial ROS production and caspase 3-dependent apoptosis and its depletion attenuated H2O2-induced apoptosis in cultured human microvascular endothelial cells (HMVECs). Bach1-induced apoptosis was largely abolished when the cells were cultured with N-acetyl-l-cysteine (NAC), a ROS scavenger. Exogenous expression of Bach1 inhibited the cell proliferation and the expression of cyclin D1, induced an S-phase arrest, and increased the expression of cyclin E2, which were partially blocked by NAC. Taken together, our results suggest that Bach1 suppresses cell proliferation and induces cell-cycle arrest and apoptosis by increasing mitochondrial ROS production, suggesting that Bach1 may be a promising treatment target for the treatment of vascular diseases.
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PMID:Bach1 Induces Endothelial Cell Apoptosis and Cell-Cycle Arrest through ROS Generation. 2705 83

The most commonly used inhalation anesthetics, sevoflurane, is reported to be a risk for development of learning disability. Erythropoietin (EPO) administration might be involved an effective therapy for sevoflurane neurotoxicity. EPO-EPO receptor-extracellular signal-related kinases 1/2 (Erk1/2) signal pathway plays a pivotal role in the neuroprotective effect. Nuclear factor erythroid 2-related factor (Nrf2)/BTB and CNC homology 1 (Bach1) ratio altering by Erk1/2 could ameliorate oxidative stress occurred in human macrophages. Primary cortical neuron cultures exposed to sevoflurane were assessed for cleaved caspase-1, cleaved caspase-3, Nrf2, Bach1, total Erk1/2, and phosphorylated Erk1/2 with the following: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT); propidium iodide uptake (PI); lactate dehydrogenase (LDH); malondialdehyde (MDA); superoxide dismutase (SOD); Real-time PCR; and Western blot. We found that sevoflurane exposure increased cell pyroptosis, apoptosis, injury, and MDA (n=9, P<0.05), but decreased cell viability (n=9, P<0.05) and down-regulated SOD (n=9, P<0.05), while EPO partially rescued the neurotoxicity induced by sevoflurane (n=9, P<0.05), as well as increase the expression of Nrf2 mRNA and Nrf2/Bach1 ratio (n=9, P<0.05). Inhibition of Erk1/2 phosphorylation via PD98059 reversed the protective effect of EPO (n=9, P<0.05). Thus, protection of EPO markedly attenuated pyroptosis and apoptosis of neurons exposed to sevoflurane via Erk1/2-Nrf2/Bach1 signal pathway.
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PMID:Erythropoietin rescues primary rat cortical neurons from pyroptosis and apoptosis via Erk1/2-Nrf2/Bach1 signal pathway. 3312 34

During breast cancer progression, tumor cells acquire multiple malignant features. The transcription factors and cell cycle regulators high mobility group A2 (HMGA2) and BTB and CNC homology 1 (Bach-1) are overexpressed in several cancers, but the mechanistic understanding of how HMGA2 and Bach-1 promote cancer development has been limited. We found that HMGA2 and Bach-1 are overexpressed in breast cancer tissues and their expression correlates positively in tumors but not in normal tissues. Individual HMGA2 or Bach-1 knockdown downregulates expression of both proteins, suggesting a mutual stabilizing effect between the two proteins. Importantly, combined HMGA2 and Bach-1 knockdown additively decrease cell proliferation, migration, epithelial-to-mesenchymal transition, and colony formation, while promoting apoptotic cell death via upregulation of caspase-3 and caspase-9. First the first time, we show that HMGA2 and Bach-1 overexpression in tumors correlate positively and that the proteins cooperatively suppress a broad range of malignant cellular properties, such as proliferation, migration, clonogenicity, and evasion of apoptotic cell death. Thus, our observations suggest that combined targeting of HMGA2 and Bach1 may be an effective therapeutic strategy to treat breast cancer.
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PMID:HMGA2 and Bach-1 cooperate to promote breast cancer cell malignancy. 3082 4

Cerebral ischemia/reperfusion (I/R) usually leads to the exacerbation of brain injury. In the present research, the effect of BTB and CNC homology 1 (BACH1) on cerebral I/R injury was studied. Mice model of middle cerebral artery occlusion/reperfusion (MCAO/R) and Neuro-2a (N2a) cell model of oxygen-glucose deprivation/reoxygenation (OGD/R) were established to investigate the role of BACH1. It was found that MCAO/R mice expressed much higher BACH1 in the brain tissues accompanied with severe cerebral infarction, whereas downregulation of BACH1 reduced the infarction in MCAO/R mice. TUNEL staining showed that the downregulation of BACH1 inhibited apoptosis in brain tissues of MCAO/R mice. The expression of cleaved caspase-3 and cleaved PARP were also decreased by the downregulation of BACH1. Reactive oxygen species (ROS) and 3-nitrotyrosine (3-NT) staining showed that the downregulation of BACH1 reduced the levels of ROS and 3-NT. Moreover, less malondialdehyde (MDA) and more superoxide dismutase (SOD), heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) were detected in MCAO/R mice pretreated with BACH1 shRNA, indicating that the downregulation of BACH1 reduced the oxidative stress. Similar conclusions were obtained from the further studies on N2a cells of OGD/R. We found that the downregulation of BACH1 reduced cell damage, oxidative stress and apoptosis in N2a cells. It was also demonstrated that the downregulation of BACH1 functioned through HO-1 and NQO1, which played important roles in protecting against cerebral I/R injury. Thus, BACH1 might be a potential therapeutic target for preventing cerebral I/R injury.
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PMID:Downregulation of BACH1 Protects AGAINST Cerebral Ischemia/Reperfusion Injury through the Functions of HO-1 and NQO1. 3231 10