Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dysregulated polymorphonuclear leukocyte (PMN) apoptosis and PMN-mediated organ damage have been associated with several medical conditions such as systemic inflammatory response syndrome (SIRS), acute respiratory distress syndrome (ARDS), and ischemia/reperfusion injury. IL-1beta and IL-8 are two cytokines that are elevated under similar conditions. Therefore, we hypothesized that PMN exposed to these cytokines would secrete factors that could affect PMN apoptosis in a cell contact-independent manner. We have previously shown that media conditioned by IL-1beta-stimulated PMN (CM-IL1beta) for 2 h suppressed spontaneous PMN apoptosis. Data presented here demonstrate that media conditioned by IL-8-stimulated PMN (CM-IL8) also have the ability to suppress spontaneous, as well as FasL- and TNF-alpha-induced apoptosis. In contrast, CM-IL1beta was able to suppress FasL-induced, but not TNF-alpha-induced, apoptosis. To elucidate the mechanisms these media use to elicit their effects, we examined the expression and function of several apoptosis-related proteins. Experimental results demonstrate that both CM-IL1beta and CM-IL8 have the ability to delay caspase activation, but have no effect on the expression of their upstream activator, Fas, or its ligand, FasL. Examination of several Bcl-2 family members revealed a selective regulation by each media: CM-IL1beta up-regulated Bcl-X(L), while CM-IL8 down-regulated Bak expression. Additionally, CM-IL1beta, but not CM-IL8, promoted the activation of NF-kappaB, which has anti-apoptotic activity. Together, we can conclude that IL-1beta- and IL-8-stimulated PMN have the ability to suppress PMN apoptosis in a paracrine manner, and that the extent and mechanism of suppression is specific for each.
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PMID:Paracrine suppression of apoptosis by cytokine-stimulated neutrophils involves divergent regulation of NF-kappaB, Bcl-X(L), and Bak. 1179 69

The effects of ischemia-reperfusion (IR) and ischemic preconditioning (IP) on hemodynamics, epicardial electrography, myocardial infarct size, cardiomyocytic apoptosis and gene proteins involving apoptosis (Fas, Bcl-2 and Bax) were observed in aneasthetized rabbit myocardium. The results are as follows. (1) During ischemia-reperfusion, heart rate, arterial blood pressure and myocardial oxygen consumption were reduced progressively. The epicardial electrographic ST-segment was elevated significantly during ischemia (P<0.001)and recovered to the baseline during reperfusion. (2) The infarct size occupied 57.7+/-2.0% of the ischemic myocardium in IR group while IP reduced the infarct size to 27.7+/-1.5% (P<0.01). (3) DNA ladder pattern of ischemic myocardium was revealed by agrose gel electrophoresis in IR group while it was not found in IP group. Apoptotic cardiomyocytes were sparse within the ischemic myocardium at risk in IP as compared with those in IR heart. Apoptosis rate of the ischemic myocardium from IR and IP groups detected by flow cytometry was 11.2+/-0.4% and 6.35+/-0.2% (P<0.01), respectively. (4) Fas and Bax protein expression in the ischemic myocardium of IR and IP groups was elevated as compared with those in non-ischemic myocardium group (P<0.05). The Fas protein expression of IR group was higher than that of IP group (P<0.05). Bcl-2/Bax ratio of IR group was lower than that in non-ischemic myocardium (P<0.01). From the results, it is suggested that IP decreases cardiomyocytic apoptosis induced by IR and this action is mediated by the reduction of Fas protein expression.
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PMID:[Ischemic preconditioning reduces cardiomyocytic apoptosis in rabbit heart in vivo]. 1195 68

Loss of germ cells is very common during various stages of mammalian spermatogenesis. Although cell death, particularly apoptosis, has been implicated, our understanding of the mechanisms underlying germ cell death is still limited. In order to elucidate the extent and mechanism of germ cell death, this review first covers what is known of germ cell degeneration in the normal testes of fetal, neonatal, and adult mice from electron microscopy (EM) and from terminal dUTP nick-end labeling (TUNEL) staining. The issue of whether the Fas and Fas ligand (FasL) system is involved in the induction of germ cell apoptosis in normal and damaged testes is then addressed, including consideration of both the ischemia-reperfusion model of testicular torsion and the estrogen-treated testis model of environmental endocrine disruption. Finally, this review proposes that different molecular pathways may be triggered to induce male germ cell apoptosis, depending upon the physiological and pathological states of the germ cells.
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PMID:Male germ cell death in mouse testes: possible involvement of Fas and Fas ligand. 1195 94

Fas ligand (FasL) is a death factor that induces apoptosis in cells bearing its receptor, Fas. Accumulating evidence indicates that the Fas/FasL system is involved not only in apoptosis but also in cell-activation signals. Recently, it was reported that local stimulation of Fas in vivo using an agonistic antibody triggers inflammatory cell infiltration and neoangiogenesis independently of apoptosis. On the other hand, Fas/FasL interaction has been proposed to control the growth and development of new subretinal vessels. Here, we evaluated the potential involvement of Fas/FasL interaction in collateral development in response to tissue ischemia. Hindlimb ischemia was induced in C57BL/6J (wild-type), B6-gld(FasL -/-), and B6-lpr(Fas -/-) mice by resection of the right femoral artery. The blood flow recovery of FasL -/- or Fas -/- mice was similar to that of wild-type mice, as determined using a laser Doppler imaging system. There was no significant difference in capillary density of the ischemic calf muscle among the mice, as determined by anti-CD31 immunostaining. We did not find any difference in the number of infiltrating inflammatory cells or in vascular endothelial growth factor expression. These results indicate that postnatal angiogenesis in response to acute ischemia can occur independently of the endogenous Fas/FasL interaction.
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PMID:Role of Fas/Fas ligand interaction in ischemia-induced collateral vessel growth. 1235 44

Fas is a widely expressed cell surface receptor that can initiate apoptosis when activated by its ligand (FasL). Whereas Fas abundance on cardiac myocytes increases in response to multiple pathological stimuli, direct evidence supporting its role in the pathogenesis of heart disease is lacking. Moreover, controversy exists even as to whether Fas activation induces apoptosis in cardiac myocytes. In this study, we show that adenoviral overexpression of FasL, but not beta-galactosidase, results in marked apoptosis both in cultures of primary neonatal cardiac myocytes and in the myocardium of intact adult rats. Myocyte killing by FasL is a specific event, because it does not occur in lpr (lymphoproliferative) mice that lack functional Fas. To assess the contribution of the Fas pathway to myocardial infarction (MI) in vivo, lpr mice were subjected to 30 min of ischemia followed by 24 h of reperfusion. Compared with wild-type mice, lpr mice exhibited infarcts that were 62.3% smaller with 63.8% less myocyte apoptosis. These data provide direct evidence that activation of Fas can induce apoptosis in cardiac myocytes and that Fas is a critical mediator of MI due to ischemia-reperfusion in vivo.
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PMID:Fas pathway is a critical mediator of cardiac myocyte death and MI during ischemia-reperfusion in vivo. 1241 49

Inhibition of mitochondrial oxidative phosphorylation progresses to uncoupling when opening of cyclosporin A-sensitive permeability transition pores increases permeability of the mitochondrial inner membrane to small solutes. Involvement of the mitochondrial permeability transition (MPT) in necrotic and apoptotic cell death is implicated by demonstrations of protection by cyclosporin A against oxidative stress, ischemia/reperfusion, tumor necrosis factor-alpha exposure, Fas ligation, calcium overload, and a variety of toxic chemicals. Confocal microscopy directly visualizes the MPT in single mitochondria within living cells from the translocation of impermeant fluorophores, such as calcein, across the inner membrane. Simultaneously, mitochondria release potential-indicating fluorophores. Subsequently, mitochondria swell, causing outer membrane rupture and release of cytochrome c and other proapoptotic proteins from the intermembrane space. In situ a sequence of decreased NAD(P)H, increased free calcium, and increased reactive oxygen species formation within mitochondria promotes the MPT and subsequent cell death. Necrotic and apoptotic cell death after the MPT depends, in part, on ATP levels. If ATP levels fall profoundly, glycine-sensitive plasma membrane permeabilization and rupture ensue. If ATP levels are partially maintained, apoptosis follows the MPT. The MPT also signals mitochondrial autophagy, a process that may be important in removing damaged mitochondria. Cellular features of necrosis, apoptosis, and autophagy frequently occur together after death signals and toxic stresses. A new term, necrapoptosis, describes such death processes that begin with a common stress or death signal, progress by shared pathways, but culminate in either cell lysis (necrosis) or programmed cellular resorption (apoptosis), depending on modifying factors such as ATP.
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PMID:Role of mitochondrial inner membrane permeabilization in necrotic cell death, apoptosis, and autophagy. 1247 May 4

Fas ligand (FasL) is a member of tumor necrosis factor family that induces apoptosis in target cells that express Fas. The function of FasL during inflammation remains controversial. In this study, we examined the role of vascular endothelial FasL during acute myocardial ischemia-reperfusion that is closely associated with inflammation. Transgenic mouse lines were established that overexpress human FasL on endothelium under the control of the vascular endothelial cadherin promoter. Expression of FasL transgene was detected at both mRNA and protein levels, and functional transgene-encoded FasL protein was specifically expressed on the surface of vascular endothelial cells. Transgenic mice developed normally and had normal hearts. When subjected to 30 min of myocardial ischemia and 72 h of reperfusion, myocardial infarct size was reduced by 42% in the transgenic mice compared with nontransgenic littermates (p < 0.05). Moreover, hemodynamic data demonstrated that transgenic hearts performed better following ischemia and reperfusion compared with nontransgenic hearts. Myocardial neutrophil infiltration was reduced by 54% after 6 h of reperfusion in transgenic hearts (p < 0.01). Neutrophil depletion prior to ischemia-reperfusion injury led to smaller infarcts that were not different between transgenic and nontransgenic mice, suggesting that endothelial FasL may attenuate ischemia-reperfusion injury by abating the inflammatory response. These results indicate that vascular endothelial FasL may exert potent anti-inflammatory actions in the setting of myocardial ischemia-reperfusion injury.
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PMID:Endothelial cell overexpression of fas ligand attenuates ischemia-reperfusion injury in the heart. 1257 84

Carbon monoxide is protective in ischemia-reperfusion organ injury, but the precise mechanisms remain elusive. We have recently shown that low levels of exogenous carbon monoxide (CO) utilize p38 MAPK and attenuate caspase 3 activity to exert an antiapoptotic effect during lung ischemia-reperfusion injury. Our current data demonstrate that CO activates the p38alpha MAPK isoform and the upstream MAPK kinase MKK3 to modulate Fas/Fas ligand expression; caspases 3, 8, and 9; mitochondrial cytochrome c release; Bcl-2 proteins; and poly(ADP-ribose) polymerase cleavage. We correlate our in vitro findings with in vivo studies using MKK3-deficient and Fas-deficient mice. Taken together, our data are the first to demonstrate that CO has an antiapoptotic effect by inhibiting Fas/Fas ligand, caspases, proapoptotic Bcl-2 proteins, and cytochrome c release via the MKK3/p38alpha MAPK pathway.
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PMID:Carbon monoxide modulates Fas/Fas ligand, caspases, and Bcl-2 family proteins via the p38alpha mitogen-activated protein kinase pathway during ischemia-reperfusion lung injury. 1269 Jan

Germ cell apoptosis is very common during various stages of mammalian testicular development. However, our understanding of the mechanisms underlying male germ cell apoptosis is still limited. This review firstly covers the general features of germ cell death in normal testes of fetal, neonatal, and adult mice from electron microscopy (EM) and terminal dUTP nick-end labeling (TUNEL) staining. The issue of whether the Fas and Fas ligand (FasL) system and/or the Bax and Bcl-2 system is involved in the induction of germ cell apoptosis in normal and damaged testes will then be addressed, including a special consideration of the ischemia-reperfusion model, the endocrine disruptor-treated model, and others. Finally, this review will propose that the process of normal spermatogenesis seems skillfull in taking advantage of apoptotic processes of germ cells and that different molecular pathways may be triggered to induce male germ cell apoptosis, depending upon the physiological and pathological states of germ cells.
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PMID:Germ cell apoptosis and its molecular trigger in mouse testes. 1270 49

Platelet activating factor (PAF) is a proinflammatory lipid mediator for inflammatory response. It is unclear whether PAF is involved in the very complex process of ischemia-reperfusion (I/R) induced mucosal apoptosis in small intestine. Intestinal I/R was induced in rats intestine by 60 min occlusion of the superior mesenteric artery, followed by a 60 min reperfusion. I/R induced mucosal apoptosis and PAF activity but inhibited PAF-acetylhydrolase activity. Increases in interleukin-6 (IL-6) and decreases in IL-10 were observed. Western blot analysis showed that I/R induced expressions of platelet endothelial cell adhesion molecule-1 (PECAM-1) and Fas and Fas ligand (FasL) proteins, cleaved Bid, and enhanced the release of cytochrome c from mitochondria to activate caspase-9. Pretreatment of PAF antagonist BN-52021 attenuated these changes, except the increase in Fas. The results showed that I/R-inhibited mucosal PAF-acetylhydrolase activity resulted in an increase of activated PAF. The activated PAF increased the mucosal IL-6 and PECAM-1, enhanced the expression of FasL but not Fas, and led to the cleavage of Bid and the release of cytochrome c from mitochondria to activate caspase-9. This finding suggests that PAF promotes mucosal apoptosis after I/R in the rat small intestine partly through FasL mediating caspase-9 active pathway.
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PMID:Platelet-activating factor promotes mucosal apoptosis via FasL-mediating caspase-9 active pathway in rat small intestine after ischemia-reperfusion. 1270 15


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