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

Recent studies suggest that mild hypothermia significantly alleviate damage following cerebral ischemia though the precise mechanism is poorly defined. In the present study, middle cerebral artery occlusion (MCAo) was induced in Sprague-Dawley (SD) rats for 1 h followed by varying periods of reperfusion. Cerebral infarcts identified by hematoxylin & eosin (H&E) staining revealed extensive lesion in normothermic (NT) 37 degrees C and small lesion in hypothermic (HT) 33 degrees C group of rats. Immunohistochemical analysis revealed Bcl-2 was induced in many neurons of HT group, while Bax and cytochrome c was induced in few neurons. In situ detection of DNA fragmentation using 3'-OH end labeling method (terminal dUTP nick-end labelling (TUNEL)) indicated, higher number of TUNEL-positive cells in NT group, but significantly decreased in HT group. The expression pattern revealed many neurons at the penumbra region could survive in HT group whereas, many neurons are committed to die in NT group. Our results suggest that hypothermia is selectively interfering at more than one place and providing protection.
 ...
PMID:Immunohistochemical expression of Bcl-2, Bax and cytochrome c following focal cerebral ischemia and effect of hypothermia in rat. 1098 40

Bcl-xL is a well characterized death-suppressing molecule of the Bcl-2 family. Bcl-xL is expressed in embryonic and adult neurons of the CNS and may play a critical role in preventing neuronal apoptosis that occurs during brain development or results from diverse pathologic stimuli, including cerebral ischemia. In this study, we used a novel approach to study the potential neuroprotective effect of Bcl-xL as a therapeutic agent in the murine model of focal ischemia/reperfusion. We created a Bcl-xL fusion protein, designated as PTD-HA-Bcl-xL, which contains the protein transduction domain (PTD) derived from the human immunodeficiency TAT protein. We demonstrated that this fusion protein is highly efficient in transducing into primary neurons in cultures and potently inhibited staurosporin-induced neuronal apoptosis. Furthermore, intraperitoneal injection of PTD-HA-Bcl-xL into mice resulted in robust protein transduction in neurons in various brain regions within 1-2 hr, and decreased cerebral infarction (up to approximately 40%) in a dose-dependent manner, as determined at 3 d after 90 min of focal ischemia. PTD-HA-Bcl-xL was effective even when it was administered after the completion of ischemia (up to 45 min), and the protective effect was independent of the changes in cerebral blood flow or other physiological parameters. Finally, as shown by immunohistochemistry, Western blotting, and substrate-cleavage assays, PTD-HA-Bcl-xL attenuated ischemia-induced caspase-3 activation in ischemic neurons. These results thus confirm the neuroprotective effect of Bcl-xL against ischemic brain injury and provide the first evidence that the PTD can be used to efficiently transduce a biologically active neuroprotectant in experimental cerebral ischemia.
 ...
PMID:In Vivo Delivery of a Bcl-xL Fusion Protein Containing the TAT Protein Transduction Domain Protects against Ischemic Brain Injury and Neuronal Apoptosis. 1209 94

Kallikrein/kinin has been shown to protect against ischemia/reperfusion-induced myocardial infarction and apoptosis. In the present study, we examined the potential neuroprotective action of kallikrein gene transfer in cerebral ischemia. Adult, male Sprague-Dawley rats were subjected to a 1-hour occlusion of the middle cerebral artery followed by intracerebroventricular injection of adenovirus harboring either the human tissue kallikrein gene or the luciferase gene. Kallikrein gene transfer significantly reduced ischemia-induced locomotor deficit scores and cerebral infarction after cerebral ischemia injury. Expression of recombinant human tissue kallikrein was identified and localized in monocytes/macrophages of rat ischemic brain by double immunostaining. Morphological analyses showed that kallikrein gene transfer enhanced the survival and migration of glial cells into the ischemic penumbra and core, as identified by immunostaining with glial fibrillary acidic protein. Cerebral ischemia markedly increased apoptotic cells, and kallikrein gene delivery reduced apoptosis to near-normal levels as seen in sham control rats. In primary cultured glial cells, kinin stimulated cell migration but inhibited hypoxia/reoxygenation-induced apoptosis in a dose-dependent manner. The effects of kinin on both migration and apoptosis were abolished by icatibant, a bradykinin B2 receptor antagonist. Enhanced cell survival after kallikrein gene transfer occurred in conjunction with markedly increased cerebral nitric oxide levels and phospho-Akt and Bcl-2 levels but reduced caspase-3 activation, NAD(P)H oxidase activity, and superoxide production. These results indicate that kallikrein gene transfer provides neuroprotection against cerebral ischemia injury by enhancing glial cell survival and migration and inhibiting apoptosis through suppression of oxidative stress and activation of the Akt-Bcl-2 signaling pathway.
 ...
PMID:Kallikrein gene transfer protects against ischemic stroke by promoting glial cell migration and inhibiting apoptosis. 1469 96

The thalamus degenerates following cerebral infarction in the territory supplied by the middle cerebral artery (MCA), and apoptosis is suspected to be the mechanism of this phenomenon. The author studied the role of the growth arrest and DNA damage-inducible gene (GADD) 153 in this thalamic degeneration. The MCA was occluded in stroke-prone spontaneously hypertensive rats. The expression of GADD 153 and Bcl-2, and the release of cytochrome c from the mitochondria to cytosol, were examined in the thalamus until 7 days after ischemia using in situ hybridization, immunoblot, immunohistochemistry and RT-PCR analyses. Gadd153 mRNA expression and GADD153 protein increased transiently at 2, 3, 5 and 7 days, and at 3 and 5 days after ischemia. Bcl-2 mRNA expression and Bcl-2 protein decreased at 3 and 5 days. The release of cytochrome c from the mitochondria was detected at 5 days. These results suggest that increased GADD 153 suppresses Bcl-2 expression, which causes the release of cytochrome c from the mitochondria and leads to thalamic degeneration.
 ...
PMID:Growth arrest and DNA damage-inducible gene 153 increases transiently in the thalamus following focal cerebral infarction. 1583 16

This experiment was designed to study the therapeutic mechanisms of Angelica on the focal cerebral ischemia injury of the rat. The ischemic area was determined by TTC stain. And terminal deoxynucleotidyl transferase (TDT) mediated DUTP-biotin nick end labeling (TUNEL) method was applied to detect neuronal apoptosis. The expressions of Bcl-2 and Bax proteins were observed by immunohistochemical staining methods. Results show that the treatment with angelica reduced the volume of cerebral infarction (p < 0.05), and that the number of neuronal apoptosis cells decreased significantly (p < 0.01). Also the expression level of Bax protein decreased (p < 0.01). These results suggest that Angelica can reduce the number of apoptosis cells by decreasing the expression of Bax protein. This is maybe one of the mechanisms of the therapeutic effect of Angelica on focal cerebral ischemia injury.
 ...
PMID:The effects of Chinese herb Angelica in focal cerebral ischemia injury in the rat. 1585 40

Stroke-induced neurological deficits and mortality are often associated with timing of treatment after the onset of stroke. We showed that local delivery of the human tissue kallikrein gene into rat brain immediately after middle cerebral artery occlusion (MCAO) exerts neuroprotection. In this study, we investigated the effect of systemic delivery of the kallikrein gene 8 hr after MCAO. Expression of recombinant human tissue kallikrein after gene transfer was identified in the ischemic brain region and blood vessels. Intravenous injection of adenovirus encoding the kallikrein gene significantly reduced neurological deficit scores 2 and 7 days after gene transfer. Kallikrein gene transfer also reduced ischemia-reperfusion (I/R)-induced cerebral infarction and promoted the survival and migration of glial cells from penumbra to the ischemic core from 3 to 14 days after gene delivery. Kallikrein reduced I/R-induced apoptosis of neuronal cells and inhibited inflammatory cell accumulation in the ischemic brain. These effects were blocked by the kinin B2 receptor antagonist icatibant. In addition, kallikrein enhanced angiogenesis and promoted neurogenesis after I/R and the stimulatory effect of kinin on neuronal cell proliferation was confirmed in primary cultured neuronal cells. The protective effects of kallikrein, through the kinin B2 receptor, were accompanied by increased cerebral nitric oxide and Bcl-2 levels, Akt phosphorylation, and reduced NAD(P)H oxidase activity, superoxide production, Bax levels, and caspase-3 activity. These results indicate that delayed systemic administration of the kallikrein gene after onset of stroke protects against ischemic brain injury by inhibiting apoptosis and inflammation and by promoting angiogenesis and neurogenesis.
 ...
PMID:Kallikrein protects against ischemic stroke by inhibiting apoptosis and inflammation and promoting angiogenesis and neurogenesis. 1645 54

Transient focal ischemia caused by middle cerebral artery occlusion (MCAo) produces apoptotic cell death in the penumbra area. Bcl-2 is a protooncogene that plays a major antiapoptotic role, at the cellular level, by counteracting the activation of apoptosis effectors, that is, caspases. It has been suggested that nitroglycerin (NTG), a nitric oxide donor, reduces ischemia/reperfusion-induced brain damage via the inhibition of caspase activity and NMDA receptor. In this chapter, we evaluated the protective effects of NTG against cerebral damage caused by transient (2h) MCAo (tMCAo) focusing our interest on the potential effects on Bcl-2 expression. Male Wistar rats were administered intraperitoneally (i.p.) with NTG (10mg/kg) or vehicle (PEG, 1ml/kg) 20min before the induction of MCAo by intraluminal silicon-coated filament (0.37-mm diameter). Cerebral infarct volume was measured 22h after reperfusion, while cortical Bcl-2 expression was evaluated at the end of 2-h MCAo (without reperfusion) and at 5h of reperfusion. The results show significant reduction of the infarct volume in rats preinjected with NTG, as compared to the vehicle group. After 2h of occlusion, no significant difference was seen in Bcl-2 expression in the ipsilateral and contralateral cortex of either experimental groups (NTG and vehicle). However, 5h after reperfusion, a significant increase of Bcl-2 expression was detected in the damaged cortex of control rats, probably reflecting a compensatory response aiming at counteracting the cell death process; this increase was absent in the NTG-treated rats. These data, while confirming the neuroprotective effect of NTG in an in vivo ischemia/reperfusion model, seem to suggest that the drug may act by downsizing the complex chain of events underlying apoptosis activation and consequent activation of antiapoptotic responses.
 ...
PMID:Neuroprotective effect of nitroglycerin in a rodent model of ischemic stroke: evaluation of Bcl-2 expression. 1767 76

Secretoneurin (SN), a neuropeptide derived from secretogranin II, promotes neurite outgrowth of immature cerebellar granule cells. SN also aids in the growth and repair of neuronal tissue, although the precise mechanisms underlying the promotion of brain tissue neuroprotection and plasticity by SN are not understood. Here, in a rat model of stroke and in ischemic human brain tissue, SN was markedly upregulated in both neurons and endothelial cells. SN-mediated neuroprotection rescued primary cortical cell cultures from oxygen/glucose deprivation. SN also induced expression of the antiapoptotic proteins Bcl-2 and Bcl-xL through the Jak2/Stat3 pathway and inhibited apoptosis by blocking caspase-3 activation. In addition, rats with occluded right middle cerebral arteries showed less cerebral infarction, improved motor performance, and increased brain metabolic activity following i.v. administration of SN. Furthermore, SN injection enhanced stem cell targeting to the injured brain in mice and promoted the formation of new blood vessels to increase local cortical blood flow in the ischemic hemisphere. Both in vitro and in vivo, SN not only promoted neuroprotection, but also enhanced neurogenesis and angiogenesis. Our results demonstrate that SN acts directly on neurons after hypoxia and ischemic insult to further their survival by activating the Jak2/Stat3 pathway.
 ...
PMID:Secretoneurin promotes neuroprotection and neuronal plasticity via the Jak2/Stat3 pathway in murine models of stroke. 1807 66

Incidence of cerebral vascular disease (CVD) is higher in patients with diabetes mellitus (DM) than that in individuals without DM, and neuronal apoptosis determines the severity of cerebral infarction. However, there is no effective therapy for CVD. Granulocyte-colony stimulating factor (G-CSF), a potent hematopoietic factor, could inhibit apoptosis of hematopoietic progenitor cells. However, its effect on neuronal cells is still unclear. In this study, we investigated the anti-apoptosis properties of G-CSF in neurons following focal cerebral ischemia in diabetic rats. The diabetic condition was generated in rats by intravenous injection of streptozotocin. After 6 weeks, diabetic rats underwent middle cerebral artery occlusion (MCAO) and received subcutaneous administration of G-CSF (50 microg/kg) daily for 7, 14 or 21 days. We analyzed the changes in neurological severity scores, infarct volume, number of apoptotic neurons, and the expression of G-CSF receptor, phosphorylated signal transducer and activator of transcription 3 (pSTAT3), cellular inhibitor of apoptosis protein 2 (cIAP2), Bcl-2, and Bax in the brain tissue. Bax is a pro-apoptotic member of the Bcl-2 protein family. The DM rats treated with G-CSF not only showed the reduced infarct volume and decreased apoptosis cell number, but also presented improved neurological scores. The G-CSF also increased the expression of pSTAT3, Bcl-2, and cIAP2 proteins as well as Bcl-2 mRNA, but inhibited Bax protein expression in the brain. These results indicate that G-CSF partially increases neuronal survival by affecting apoptosis pathways. G-CSF provides a potential treatment for stroke and other neurological dysfunction accompanied by neuronal apoptosis.
 ...
PMID:Granulocyte-colony stimulating factor inhibits neuronal apoptosis in a rat model of diabetic cerebral ischemia. 1883 93

Ischemic brain is particularly susceptible to free radicals mediated secondary neuronal damage, especially mitochondrial dysfunctions. Chinese Herbal Medicine with antioxidant properties is believed to have potential therapeutic effect. Leonurine, an alkaloid present in Herba Leonuri (HL), has shown biological effects such as antioxidant, anticoagulant, anti-apoptosis and protection against ischemic heart disease. In this study, neuroprotective effects of leonurine against cerebral ischemia/reperfusion-induced mitochondrial dysfunctions in cortex were evaluated. We used transient rat middle cerebral artery occlusion (MCAO) model of brain ischemia. The rats were treated with their respective treatments for 1 week prior to the MCAO. We found that leonurine significantly improved neurological outcome and reduced ischemia/reperfusion (I/R)-induced cerebral infarction 24 h after MCAO. Leonurine decreased reactive oxygen species (ROS) level in mitochondria isolated from ischemic cortex, which was increased by MCAO. Terminal deoxyuridine triphosphate (dUTP) Nick-End Labeling (TUNEL) staining showed anti-apoptotic effect of leonurine on ischemic cortex. Western blot analysis showed a marked decrease in the expression of Bax and an increase of Bcl-2 as a result of leonurine treatment. The attenuation of mitochondrial membrane swelling, restore of mitochondrial membrane potential and content of cytochrome c (Cyt-C) in mitochondria isolated from ischemic cortex could also be observed in leonurine treated group. The findings of this study suggest that leonurine has promising therapeutic effect for ischemic stroke treatment through antioxidant and anti-apoptotic mechanisms.
 ...
PMID:Neuroprotective effects of leonurine on ischemia/reperfusion-induced mitochondrial dysfunctions in rat cerebral cortex. 2113 33


1 2 3 4 5 6 7 Next >>