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

Administration of the VEGF receptor blocker SU5416 to rats causes alveolar septal cell apoptosis and emphysema; both can be prevented by a superoxide dismutase mimetic. Here we show that SU5416 induces the expression of heme oxygenase-1 in the lung tissue and that administration of antioxidant N-acetyl-l-cysteine protects alveolar septal cells against apoptosis, as demonstrated by caspase-3 lung immunohistochemistry, and against emphysema.
COPD 2004 Apr
PMID:N-acetylcysteine treatment protects against VEGF-receptor blockade-related emphysema. 1699 36

Chronic inflammation, imbalance of proteolytic and anti-proteolytic activities, oxidative stress, and apoptosis of lung structural cells contribute to the pathogenesis of COPD. Prostacyclin protects cells against apoptosis, has anti-inflammatory properties, partially prevents cigarette smoke extract (CSE)-induced apoptosis of the pulmonary endothelium, and thus may be relevant in the pathogenesis of emphysema. We determined whether a synthetic stable prostacyclin analog, beraprost sodium (BPS), attenuates the development of CSE-induced emphysema and elucidated the molecular mechanisms involved in its effect. Sprague-Dawley rats were treated with BPS and injected with CSE once a week for 3 wk. We measured the DNA damage of cells, the expression of caspase-3, and the activity of matrix metalloproteinase (MMP)-2 and MMP-9. We also analyzed TNFalpha and IL-1beta concentrations and the serum antioxidant activity. BPS prevented the development of CSE-induced emphysema, resulting in significant attenuation in alveolar enlargement and pulmonary parenchymal destruction. BPS inhibited pulmonary apoptosis and induction of MMP-2 and MMP-9 activity. Moreover, the protective effect of BPS was associated with a reduction of the expression of proinflammatory cytokines including TNFalpha and IL-1beta and a normalized biological oxidant activity. BPS introduces all these events, probably by activating cAMP signaling through acting specific prostacyclin receptors. In conclusion, BPS protects against the development of CSE-induced emphysema by attenuating apoptosis, inhibiting proteolytic enzyme activity, reducing inflammatory cytokine levels, and augmenting antioxidant activity. BPS may potentially represent a new therapeutic option in the prevention of emphysema in humans in prospect.
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PMID:Protective effect of beraprost sodium, a stable prostacyclin analog, in the development of cigarette smoke extract-induced emphysema. 1920 16

Toll-like receptors (TLRs) exert important nonimmune functions in lung homeostasis. TLR4 deficiency promotes pulmonary emphysema. We examined the role of TLR4 in regulating cigarette smoke (CS)-induced autophagy, apoptosis, and emphysema. Lung tissue was obtained from chronic obstructive lung disease (COPD) patients. C3H/HeJ (Tlr4-mutated) mice and C57BL/10ScNJ (Tlr4-deficient) mice and their respective control strains were exposed to chronic CS or air. Human or mouse epithelial cells (wild-type, Tlr4-knockdown, and Tlr4-deficient) were exposed to CS-extract (CSE). Samples were analyzed for TLR4 expression, and for autophagic or apoptotic proteins by Western blot analysis or confocal imaging. Chronic obstructive lung disease lung tissues and human pulmonary epithelial cells exposed to CSE displayed increased TLR4 expression, and increased autophagic [microtubule-associated protein-1 light-chain-3B (LC3B)] and apoptotic (cleaved caspase-3) markers. Beas-2B cells transfected with TLR4 siRNA displayed increased expression of LC3B relative to control cells, basally and after exposure to CSE. The basal and CSE-inducible expression of LC3B and cleaved caspase-3 were elevated in pulmonary alveolar type II cells from Tlr4-deficient mice. Wild-type mice subjected to chronic CS-exposure displayed airspace enlargement;, however, the Tlr4-mutated or Tlr4-deficient mice exhibited a marked increase in airspace relative to wild-type mice after CS-exposure. The Tlr4-mutated or Tlr4-deficient mice showed higher levels of LC3B under basal conditions and after CS exposure. The expression of cleaved caspase-3 was markedly increased in Tlr4-deficient mice exposed to CS. We describe a protective regulatory function of TLR4 against emphysematous changes of the lung in response to CS.
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PMID:TLR4 deficiency promotes autophagy during cigarette smoke-induced pulmonary emphysema. 2298 53

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are considered attractive therapeutic agents for the treatment of COPD. However, little is known about the impact of Notch on the proliferation, migration, and survival of MSCs in a cigarette smoke (CS) microenvironment. Here, we used CS extract to mimic the CS microenvironment in vitro, with the intention to investigate the effect of Notch in regulating proliferation, migration, and survival of BM-MSCs. Rat bone marrow mesenchymal stem cells were infected with lentivirus vector containing the intracellular domain of Notch1 (N1ICD) and challenged with CS extract. Cell proliferation was detected by Ki67 staining and expression of cell cycle-related proteins. A transwell assay was used to measure cell migration and the expression of apoptotic proteins was examined. The proliferation of BM-MSCs overexpressing N1ICD significantly increased. Consistently, levels of cyclin D1, p-Rb, and E2F-1 increased in N1ICD overexpressing cells. N1ICD overexpression also increased cell migration compared with the control group. N1ICD overexpression equilibrated the expression of Bax and Bcl-2, and blocked caspase-3 cleavage, contributing to the inhibition of apoptosis. Moreover, blockade of the PI3K/Akt pathway suppressed the aforementioned cytoprotective effects of N1ICD. In conclusion, activation of Notch signaling improved proliferation, migration, and survival of BM-MSCs in a CS microenvironment partly through the PI3K/Akt pathway.
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PMID:Activation of Notch1 signaling alleviates dysfunction of bone marrow-derived mesenchymal stem cells induced by cigarette smoke extract. 2913 45

COPD is a chronic airway inflammatory disease characterized mainly by neutrophil airway infiltrations. The neutrophil airway inflammation is mainly mediated through a key player like the pro-inflammatory cytokine IL-17A which is involved in the modulation of p53-fibrinolytic system. This study was undertaken to examine the molecular changes for the expressions of IL-17A and p53-fibrinolytic system in smokers with or without COPD. Blood and serum samples were collected from ten patients of smokers having COPD and ten samples from smokers without COPD and ten healthy control subjects. Western blot analyses were performed to evaluate the expressions of IL-17A, p53 and PAI-1. Apoptosis was assessed by immunoblot for cleaved caspase-3. In addition, FEV% was also determined of these patients. qRT-PCR was done to detect the gene expression study from the blood samples on p53-fibrinolytic components. A significant difference was found in the expression levels of IL-17A in smokers with COPD patient when compared to smokers without COPD and the control subjects. Similarly the smokers with COPD showed significant increase in the fibrinolytic component PAI-1 as well as in expression levels of p53 when compared to smokers without COPD and normal subjects. Increased cleaved caspase-3 may also promote apoptosis.The expression pattern of the IL-17A in chronic obstructive pulmonary distress syndrome samples was increased as compared of those of normal samples, and their main role in the regulation of and p53-fibrinolytic system makes these components as a predictive prominent component in smokers with COPD.
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PMID:Changes in the expression level of IL-17A and p53-fibrinolytic system in smokers with or without COPD. 3025 Sep 95

Cardiac microvascular damage, which is often caused by anoxia and hypoglycemia, is associated with the development of cardiac injury. DJ-1 encodes a peptidase C56 protein family related protein, is has been linked to oxidative stress in various cells such as neurons, COPD epithelial cells, and macrophages. However, the effect of DJ-1 towards oxidative stress caused by anoxia and hypoglycemia of cardiac microvascular endothelial cells (CMEC) remains unclear. In this study, we investigated the role and underlying molecular mechanism of DJ-1 in CMEC with anoxia/hypoglycemic (A/H) injury. We found that the mRNA and the protein expression of DJ-1 in CMEC with A/H injury were significantly downregulated. DJ-1 overexpression by pcDNA.3.1-DJ-1 transfection elevated cell viability while it inhibited LDH leakage, cell apoptosis, caspase-3 activity, ROS level, and MDA contents, while knockdown of DJ-1 has the opposite results. In addition, tube formation was increased in DJ-1 overexpression, while it was decreased in DJ-1 knockdown CMEC with A/H injury. In addition, our results indicated that DJ-1 can regulate glutathione (GSH) levels by modulating AKT activity in CMEC with A/H injury. The downregulation of AKT and GSH may remove the protective role of DJ-1 against A/H injury in CMEC. Taken together, this study showed that DJ-1 upregulation protected CMEC against A/H injury via the AKT/GSH signaling pathway.
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PMID:DJ-1 alleviates anoxia and hypoglycemia injury in cardiac microvascular via AKT and GSH. 3244 81