Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using a rat model of moderate hypothermic (26 degrees C-28 degrees C) cardiopulmonary bypass (CPB) with hemodilution, we investigated hippocampal apoptotic gene expression and neuronal apoptosis up to 6 h after CPB. The CPB was performed on male rats (380-400 g) under general anesthesia with isoflurane and fentanyl. The right atrium and tail artery were cannulated, and a peristaltic pump and membrane oxygenator were used for CPB. Two groups were studied: Group 1 consisted of fasted rats (n = 15) subjected to 60 min of moderate hypothermic nonpulsatile CPB; Group 2 consisted of sham-operated rats (n = 15). At 1 h after CPB, in 6 rats per group, hippocampus was processed for the apoptotic gene (bcl-2 and bax) messenger RNAs detection by reverse transcriptase polymerase chain reaction, and messenger RNA expression was determined by the ratio of the polymerase chain reaction product of bcl-2 or bax to the beta-actin gene. At 6 h after CPB, in 6 rats per group, hippocampus expression of Bcl-2 and bax protein was determined by immunohistochemistry, and neuronal apoptosis was detected by TUNEL. At 6 h after CPB, in three rats per group, changes in hippocampal CA1 neuronal ultra structure were determined with electron microscopy. Group 1 had increased ratios of bcl-2/beta-actin, bax/beta-actin, and bax/bcl-2 mRNA at 1 h after CPB (bcl-2/beta-actin, 0.82 +/- 0.14 versus 0.63 +/- 0.07; P = 0.03; bax/beta-actin, 1.04 +/- 0.14 versus 0.56 +/- 0.03; P = 0.00; bax/bcl-2, 1.31 +/- 0.12 versus 0.84 +/- 0.09; P = 0.02; Group 1 versus Group 2, respectively). Group 1 had increased bcl-2 and bax protein expression in hippocampal CA1 region at 6 h after CPB (bcl-2, 0.18 +/- 0.05 versus 0.09 +/- 0.01; P = 0.02; bax, 0.20 +/- 0.06 versus 0.04 +/- 0.02; P = 0.01; Group 1 versus Group 2, respectively). Group 1 had increased TUNEL staining in hippocampus CA1 at 6 h after CPB (0.14 +/- 0.02 versus 0.03 +/- 0.01; P = 0.00; Group 1 versus Group 2, respectively). In Group 1 CA1 hippocampus neurons, ultra-structural changes consistent with apoptosis occurred. In rats, moderate hypothermic CPB with hemodilution is associated with CA1 hippocampus bax and bcl-2 gene expression and neuronal apoptosis during the early post-CPB recovery period.
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PMID:Hippocampus bcl-2 and bax expression and neuronal apoptosis after moderate hypothermic cardiopulmonary bypass in rats. 1655 91

The rostral ventrolateral medulla (RVLM) is the origin of a 'life-and-death' signal that reflects central cardiovascular regulatory failure during brain stem death. Using an experimental endotoxaemia model, we evaluated the hypothesis that the 60 kDa heat shock protein 60 (HSP60) reduces cardiovascular fatality during brain stem death via an anti-apoptotic action in the RVLM. In Sprague-Dawley rats maintained under propofol anaesthesia, proteomic or Western blot analysis revealed a progressive augmentation of HSP60 expression in the RVLM after intravenous administration of Escherichia coli lipopolysaccharide (30 mg kg(-1)). Pretreatment with a microinjection of actinomycin D or cycloheximide into bilateral RVLM significantly blunted this HSP60 increase, whereas real-time PCR showed progressive augmentation of hsp60 mRNA. Intriguingly, superimposed on the augmented expression was a progressive decline in mitochondrial, or elevation in cytosolic, HSP60 in ventrolateral medulla. Loss-of-function manipulations in the RVLM using anti-HSP60 antiserum or antisense hsp60 oligonucleotide exacerbated mortality by potentiating the cardiovascular depression during experimental endotoxaemia, alongside intensified nucleosomal DNA fragmentation, elevated cytoplasmic histone-associated DNA fragments or augmented cytochromec-caspase-3 cascade of apoptotic signalling in the RVLM. Immunoprecipitation coupled with immunoblot analysis further revealed a progressive increase in the complex formed between HSP60 and mitochondrial or cytosolic Bax or mitochondrial Bcl-2 during endotoxaemia, alongside a dissociation of the cytosolic HSP60-Bcl-2 complex. We conclude that HSP60 redistributed from mitochondrion to cytosol in the RVLM confers neuroprotection against fatal cardiovascular depression during endotoxaemia via reduced activation of the cytochrome c-caspase-3 cascade of apoptotic signalling through enhanced interactions with mitochondrial or cytosolic Bax or Bcl-2.
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PMID:Heat shock protein 60 in rostral ventrolateral medulla reduces cardiovascular fatality during endotoxaemia in the rat. 1667 90

Pharmacological modulation of heme oxygenase (HO) gene expression may have significant therapeutic potential in oxidant-induced disorders, such as ischemia reperfusion (I/R) injury. Higenamine is known to reduce ischemic damages by unknown mechanism(s). The protective effect of higenamine on myocardial I/R-induced injury was investigated. Ligation of rat left anterior descending coronary artery for 30 min under anesthesia was done and followed by 24 h reperfusion before sacrifice. I/R-induced myocardial damages were associated with mitochondria-dependent apoptosis as evidenced by the increase of cytochrome c release and caspase-3 activity. Administration of higenamine (bolus, i.p) 1 h prior to I/R-injury significantly decreased the release of cytochrome c, caspase-3 activity, and Bax expression but up-regulated the expression of Bcl-2, HO-1, and HO enzyme activity in the left ventricles, which were inhibited by ZnPP IX, an enzyme inhibitor of HO-1. In addition, DNA-strand break-, immunohistochemical-analysis, and TUNEL staining also supported the anti-apoptotic effect of higenamine in I/R-injury. Most importantly, administration of ZnPP IX inhibited the beneficial effect of higenamine. Taken together, it is concluded that HO-1 plays a core role for the protective action of higenamine in I/R-induced myocardial injury.
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PMID:Higenamine reduces apoptotic cell death by induction of heme oxygenase-1 in rat myocardial ischemia-reperfusion injury. 1670 64

Osteopontin (OPN) is expressed in many tissues during inflammatory responses. After spinal cord injury, microglia expresses OPN at the site of injury during the early to subacute stages. However, the function of OPN in spinal cord injury is not well understood. This study examines the responses of OPN knock-out (KO) and wild-type (WT) mice to spinal cord contusion injury. KO and WT mice were injured with a modified New York University impactor. Weights of 10 or 5.6 g were dropped 6.25 mm onto the T13 spinal cord under isoflurane anesthesia. At 24 h, homogenized spinal cords were analyzed for total potassium concentration to estimate lesion volumes. Expression of apoptotic genes, proinflammatory cytokines, and nerve growth factors was measured by reverse transcription (RT)-PCR and Western blot. In a series of animals, locomotor recovery was assessed with the Basso mouse scale (BMS) for 6 weeks, and histological analyses was performed to determine tissue preservation. Lesion volume showed no significant differences between KO and WT mice at 24 h. RT-PCR indicated that KO mice had significantly less Bcl-2, tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 mRNA compared with WT controls. Western blot also showed that KO had significantly less Bcl-2 7 d after spinal cord injury. KO mice had significantly worse BMS locomotor scores than WT at 6 weeks. KO mice also had a significantly reduced area of spared white matter and fewer neuronal-specific nuclear protein-positive neurons in the spinal cord surrounding the impact site. This result supports a potential neuroprotective role for OPN in the inflammatory response to spinal cord injury.
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PMID:Osteopontin-deficient mice exhibit less inflammation, greater tissue damage, and impaired locomotor recovery from spinal cord injury compared with wild-type controls. 1739 76

Despite major advances in treating patients with coronary heart disease, reperfusion injury is still considered to be a major problem, especially in surgical settings. Here, we demonstrate the protective effects of a novel bisindolylmaleimide derivative, MS1 (2-[1-(3-aminopropyl)indol-3-yl]-3-(indol-3-yl)-N-methylmaleimide), against reperfusion injury of the heart. After anesthesia and artificial ventilation, Wistar rats were subjected to 30 min of left coronary artery occlusion followed by 120 min of reperfusion with or without treating the rats with MS1 (2.25 mumol.L-1.kg-1) before left coronary artery occlusion. Compared with the untreated hearts, MS1 treatment significantly reduced myocardial infarct size (35.1% +/- 3% vs. 75.5% +/- 5%, p < 0.001), reduced prevalence of apoptotic cells (2.6% +/- 0.5% vs. 12.2% +/- 2.1%, p < 0.001), prevented mitochondrial swelling and cytochrome c release, inhibited downregulation of antiapoptotic protein Bcl-2 expression, and suppressed caspase-3 activation. In contrast, pretreatment with atractyloside, a mitochondrial permeability transition pore opener, abolished the protective effects of MS1. In conclusion, MS1 inhibits pathologic opening of permeability transition pores and protects the heart against reperfusion injury and pathologic apoptosis.
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PMID:Novel bisindolylmaleimide derivative inhibits mitochondrial permeability transition pore and protects the heart from reperfusion injury. 1806 98

The aim of this study was to investigate the effects of paeoniflorin (PF) and paeonol (PN), the main active compounds of the Paeonia albiflora Pallas, on myocardial ischemia and reperfusion (I/R)-induced injury in Sprague-Dawley rats IN VIVO. Under anesthesia, the rats were subjected to 25 min of ischemia by ligation of the left anterior descending coronary artery (LAD) followed by 6 h (Western blot analysis) or 24 h (hemodynamics and infarct size) of reperfusion. When the infarct size was measured as the percentage of the area at risk, both PF (25.0 % +/- 7.0 %) and PN (24.1 % +/- 5.5 %) significantly (P < 0.05) reduced it compared to I/R control (54.8 % +/- 2.6 %). Administration of 10 mg/kg PF or PN 1 h prior to I/R injury also resulted in a significant improvement of the hemodynamic parameters. Furthermore, both PF and PN decreased the caspase-3 and Bax expressions but up-regulated Bcl-2 in the left ventricles. The results show that both PF and PN reduced myocardial damage in rat through protection from apoptosis, suggesting that Paeonia albiflora Pallas might be useful in treating myocardial infarction.
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PMID:Paeonol and paeoniflorin, the main active principles of Paeonia albiflora, protect the heart from myocardial ischemia/reperfusion injury in rats. 1820 54

During inhalation anaesthesia lung epithelial cells are directly exposed to halogenated hydrocarbons such as halothane. Information about the effects of volatile anaesthetics on lung cells is rather limited although their noxious effect on the A549 alveolar cells has been shown recently. The present study indicated that halothane decreases cell viability, impairs DNA integrity and provokes stress-induced apoptosis in A549 cells when applied at clinically relevant concentrations. Data obtained clearly demonstrated intensive expression of anti-apoptotic Bcl-2 protein during treatment with all tested concentrations. In post-treatment periods the increased DNA injury was accompanied by reduction of Bcl-2 expression. We concluded that the in vitro effect of halothane on lung cells involved alteration in the expression of proteins of the mitochondrial apoptotic pathway.
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PMID:Mitochondria are involved in stress response of A549 alveolar cells to halothane toxicity. 1826 50

This study was designed to evaluate the effect of long-term pretreatment with celecoxib, a cyclooxygenase-2 inhibitor, on myocardial infarct size. Celecoxib (3 mg/kg/day i.p; n = 16) or vehicle (DMSO 50%; EtOH 15%; distilled water, n = 16) was administered chronically to male Sprague-Dawley rats through ALZET osmotic pumps for 28 days. Under anaesthesia, the animals were then subjected to left anterior descending coronary artery occlusion for 40 minutes, followed by 24-hour reperfusion. The results show that myocardial infarct size in celecoxib-treated rats was significantly reduced compared to the control group (37.5 +/- 2.5% versus 48.0 +/- 2.6% of the area at risk, P < 0.05, n = 10 per group). Accumulation of neutrophils, estimated by myeloperoxidase levels, indicated an increase in the ischemic area without any significant difference between groups. No significant difference was observed between the treated and vehicle groups in terms of plasma prostaglandin E2 and tumour necrosis factor-alpha. Apoptosis, evaluated by Bax/Bcl-2 and terminal dUTP nick-end labelled-positive cells, was significantly decreased in the subendocardial layer of the ischemic area in celecoxib-treated rats. This study indicates that pretreatment with celecoxib can reduce infarct size by a mechanism, which may involve apoptosis inhibition.
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PMID:Chronic pretreatment with celecoxib reduces infarct size. 1952 17

Diabetes mellitus has been known to mitigate ischemic or pharmacologic preconditioning in ischemia-reperfusion injuries. Remifentanil is a widely used opioid in cardiac anesthesia that possesses a cardioprotective effect against ischemia-reperfusion. We evaluated whether diabetes affected remifentanil preconditioning induced cardioprotection in ischemia-reperfusion rat hearts in view of anti-apoptotic pathways of survival and Ca(2+) homeostasis. Streptozotocin-induced, diabetic rats and age-matched wild-type Sprague-Dawley rats were subjected to a left anterior descending coronary artery occlusion for 30min followed by 1h of reperfusion. Each diabetic and wild-type rat was randomly assigned to the sham, ischemia-reperfusion only, or remifentanil preconditioning group. Myocardial infarct size, activities of ERK1/2, Bcl2, Bax and cytochrome c, and gene expression influencing Ca(2+) homeostasis were assessed. Remifentanil preconditioning significantly reduced myocardial infarct size compared to ischemia-reperfusion only in wild-type rats but not in diabetic rats. Remifentanil preconditioning increased expression of ERK1/2 and anti-apoptotic protein Bcl-2 and decreased expression of pro-apoptotic proteins, Bax and cytochrome c, compared to ischemia-reperfusion only in wild-type rats. In diabetic rat hearts, however, remifentanil preconditioning failed to recover the phosphorylation state of ERK1/2 and to repress apoptotic signaling. In addition, diabetes minimized remifentanil induced modulation of abnormal changes in sarcoplasmic reticulum genes and proteins in ischemia-reperfusion rat hearts. In conclusion, diabetes mitigated remifentanil induced cardioprotection against ischemia-reperfusion, which might be associated with reduced recovery of the activities of proteins involved in anti-apoptotic pathways including ERK1/2 and the abnormal expression of sarcoplasmic reticulum genes as a result of ischemia-reperfusion in rat hearts.
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PMID:Diabetes mellitus mitigates cardioprotective effects of remifentanil preconditioning in ischemia-reperfused rat heart in association with anti-apoptotic pathways of survival. 1994 81

Autophagy has been implicated in cardiac cell death during ischemia/reperfusion (I/R). In this study we investigated how propofol, an antioxidant widely used for anesthesia, affects the autophagic cell death induced by the myocardial I/R injury. The infarction size in the myocardium was dramatically reduced in rats treated with propofol during I/R compared with untreated rats. A large number of autophagic vacuoles were observed in the cardiomyocytes of I/R-injured rats but rarely in I/R-injured rats treated with propofol. While LC3-II formation, an autophagy marker, was up-regulated in the I/R-injured myocardium, it was significantly down-regulated in the myocardial tissues of I/R-injured and propofol-treated rats. Moreover, propofol inhibited the I/R-induced expression of Beclin-1, and it accelerated phosphorylation of mTOR during I/R and Beclin-1/Bcl-2 interaction in cells, which indicates that it facilitates the inhibitory pathway of autophagy. These data suggest that propofol protects the autophagic cell death induced by the myocardial I/R injury.
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PMID:Propofol protects the autophagic cell death induced by the ischemia/reperfusion injury in rats. 2082 Oct 58


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