Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:A9QXG9 (bcl-2)
 7,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The potential role of inflammatory mechanisms in the pathophysiology of ischemic brain damage has intensely been discussed. We have recently demonstrated that stroke patients display an intrathecal production of proinflammatory cytokines early after onset of symptoms. IL-1beta, one of these cytokines, stimulates the production of nitric oxide (NO), a potent inflammatory mediator. The aim of the present study was to investigate the intrathecal levels of nitrate, one of the main metabolites of NO in acute stroke and to relate its levels to brain damage. Stroke patients were prospectively studied with clinical evaluation, radiological assessment and analysis of intrathecal levels of nitrate by gas chromatography/mass spectrometry. In addition, simultaneous analyses of cytokines and of soluble Fas/APO-1 and bcl-2, two proteins regulating apoptosis, were performed. The intrathecal levels of nitrate were not significantly different in stroke patients compared to controls throughout the observation period. However, the intrathecal levels of nitrate increased significantly 3 months after stroke onset compared with the first 3 days. Interestingly, the levels of nitrate measured at stroke onset were negatively correlated to the final size of infarct volume (r = -0.69, p < 0.05) measured by MRI. In addition, patients with large infarcts displayed significantly (p = 0.008) lower levels of nitrate in cerebrospinal fluid compared to patients with small infarcts during the first 3 days after stroke onset. In contrast, the intrathecal levels of nitrate were significantly positively correlated (r = 0.79, p < 0. 001) to the neurological deficit and negatively correlated (r = -0. 76, p < 0.05) to bcl-2, a protein downregulating neuronal apoptosis, in the late stage of the stroke. Early NO production is associated with a smaller infarct volume, suggesting a protective effect, whereas late NO production is associated with severer neurological deficits, suggesting a neurotoxic effect. Treatment trials pertaining to modulate NO production in stroke should take into consideration the dual effect of NO on ischemic brain damage.
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PMID:Intrathecal release of nitric oxide and its relation to final brain damage in patients with stroke. 1077 46

Although prostaglandin (PG) F2alpha is known to be a principal luteolytic factor, its action on the bovine corpus luteum (CL) is mediated by other intra-ovarian factors. Tumor necrosis factor-alpha (TNFalpha) and its specific receptors are present in the bovine CL with the highest expressions at luteolysis. TNFalpha in combination with interferon-gamma reduced progesterone (P4) secretion, increased PGF2alpha and leukotriene C4 (LTC4) production, and induced apoptosis of the luteal cells in vitro. Low concentrations of TNFalpha caused luteolysis, which resulted in a decreased level of P4, and increased levels of PGF2alpha, LTC4 and nitrite/nitrate (stable metabolites of nitric oxide-NO) in the blood. Inhibition of local NO production counteracts spontaneous and PGF2alpha-induced luteolysis. Therefore, NO is a likely candidate for the molecule that mediates PGF2alpha and TNFalpha actions during luteolysis. Both PGF2alpha and TNFalpha increase NO concentrations in blood, and stimulate NO synthase expression on protein level in the bovine CL cells. NO stimulates PGF2alpha and LTC4 secretion, inhibits P4 production and reduces the number of viable luteal cells. TNFalpha and NO induce apoptotic death of the CL by modulating expression of bcl-2 family genes and by stimulating expression and activity of caspase-3. The above findings indicate that TNFalpha and NO play crucial roles in functional and structural luteolysis in cattle.
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PMID:Role of tumor necrosis factor-alpha and nitric oxide in luteolysis in cattle. 1595 Apr 30

The complex of lanthanum (III) was synthesized reacting the respective inorganic salt with 5-aminoorotic acid in amounts equal to the metal:ligand molar ratio of 1:3. The complex was prepared by adding an aqueous solution of lanthanum (III) nitrate to an aqueous solution of the ligand, subsequently raising the pH of the mixture gradually to approx. 5.0 through addition of a dilute solution of sodium hydroxide. The structure of the final complex was determined by means of spectral data (IR, Raman,( 1)H-NMR) and elemental analysis. Significant differences in the IR spectrum of the complex were observed as compared to the spectrum of the ligand. A comparative analysis of the Raman spectrum of the complex with that of the free 5-aminoorotic acid allowed a straightforward assignment of the vibrations of the ligand groups involved in coordination. The ligand and the complex were tested for the cytotoxic activities on the chronic myeloid leukemia derived K-562, overexpressing the BCR-ABL fusion protein and the non-Hodgkin lymphoma derived DOHH-2, characterized by a re-expression of the anti-apoptotic protein bcl-2 cell lines. The results obtained indicate that the tested compounds exerted a considerable cytotoxic activity upon the evaluated cell lines in a concentration-dependent matter, which enabled the construction of dose-response curves and the calculation of the corresponding IC(50 )values. The inorganic salt exerted a very weak cytotoxic effect on these cells, which is in contrast to the lanthanum (III) complex.
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PMID:New lanthanum (III) complex--synthesis, characterization, and cytotoxic activity. 1704 90

The molecular mechanisms by which nickel compounds cause immune cytotoxicity are far from understood. Our preliminary data suggested that nickel(II) induced apoptosis in Jurkat cells by mitochondrial pathway, specifically via mitochondrial membrane potential dissipation and antiapoptotic gene bcl-2 down-regulation. The main goal of this study was to further investigate the toxicity of nickel, especially the induction of reactive oxygen species (ROS) on immune cells, which finally induced apoptosis. Nickel was found to induce glutathione (GSH) depletion in a dose- and time-dependent manner. When Jurkat cells were preincubated with antioxidant N-acetylcysteine (NAC), apoptosis was inhibited distinctly, which suggested that ROS played an initial role in nickel immune toxicity. Heme oxygenase-1 (HO-1) and Nitric oxide (NO) which may play an important role in regulatory and protective processes in cells were assayed upon nickel treatment. A significant increase in HO-1 mRNA levels was detected in nickel treated cells. We confirmed that reduction of Nitrate levels in Jurkat cells was due to down-regulation of inducible nitric oxide synthase (iNOS), not endothelial nitric oxide synthase (eNOS). Expression changes of HO-1 and iNOS were markedly blocked when Jurkat cells were preincubated with NAC, suggesting that ROS resulted in HO-1 and iNOS dysfunction in Jurkat cells. We supposed that the immune toxicity of nickel(II) was mainly due to GSH depletion and finally led to apoptosis, probably via changing the expression levels of HO-1 and iNOS in human T lymphocytes.
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PMID:GSH-dependent iNOS and HO-1 mediated apoptosis of human Jurkat cells induced by nickel(II). 1883 Sep 72

Neonatal rat cardiomyocytes were subjected to 24 h of hypoxia 95%N2/5%CO2 and 24 h of hypoxia plus 4 h of reoxygenation 95%O2/5%CO2. 24 h of hypoxia increased the levels of NO, NO2-/NO3-, TBARS and LDH. 24 h of hypoxia plus 4 h of reoxygenation decreased the levels of NO, NO2-/NO3-, but further increased TBARS and LDH. The hypoxia up-regulated the expression of bcl-2, p53 and p21/waf1/cip1 but the reoxygenation down-regulated the expression of bcl-2, and further up-regulated p53 and p21/waf1/cip1. The hypoxia increased cell apoptosis and reoxygenation further increased both apoptotic and necrotic cell death. NO, NO2-/NO3- TBARS, DNA fragmentation and cell apoptosis were enhanced by SNP and inhibited by L-NAME respectively. In addition, SOD/catalase down-regulated the expression of p53, p21/wafl/cipl and TBARS but up-regulated bcl-2 and increased indirectly the level of NO, NO2-/NO3-, and inhibited DNA fragmentation. The results suggest that hypoxia-induced cell death is associated with the activation of NO, bcl-2 and p53 pathway, while hypoxia-reoxygenation induced cell death via the generation of reactive oxygen species and activation of p53 pathway. The present study clarified that NO may be an initiative signal to apoptotic cell death and the activation of bcl-2, p53 and p21/waf1/cip1 pathway in hypoxic and hypoxia-reoxygenated cardiomyocytes.
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PMID:Nitric oxide and oxygen radicals induced apoptosis via bcl-2 and p53 pathway in hypoxia-reoxygenated cardiomyocytes. 2021 59

Aging is a progressive process related to the accumulation of oxidative damage and neuroinflammation. We tried to find the anti-amnesic effect of the Scutellaria baicalens Georgia (SBG) ethanol extract and its major ingredients. The antioxidative effect of SBG on the mice model with memory impairment induced by chronic injection of D-galactose and sodium nitrate was studied. The Y-maze test was used to evaluate the learning and memory function of mice. The activities of superoxide dismutase, catalase and the content of malondialdehyde in brain tissue were used for the antioxidation activities. Neuropathological alteration and expression of bcl-2 protein were investigated in the hippocampus by immunohistochemical staining. ROS, neuroinflammation and apoptosis related molecules expression such as Cox-2, iNOS, procaspase-3, cleaved caspase-3, 8 and 9, bcl-2 and bax protein and the products of iNOS and Cox-2, NO, PGE2, were studied using LPS-activated Raw 264.7 cells and microglia BV2 cells. The cognition of mice was significantly improved by the treatment of baicalein and 50 and 100 mg/kg of SBG in Y-maze test. Both SBG groups showed strong antioxidation, antiinflammation effects with significantly decreased iNOS and Cox-2 expression, NO and PGE2 production, increased bcl-2 and decreased bax and cleaved caspase-3 protein expression in LPS induced Raw 264.7 and BV2 cells. We also found that apoptotic pathway was caused by the intrinsic mitochondrial pathway with the decreased cleaved caspase-9 and unchanged cleaved caspase-8 expression. These findings suggest that SBG, especially high dose, 100 mg/kg, improved the memory impairments significantly and showed antioxidation, antiinflammation and intrinsic caspase-mediated apoptosis effects.
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PMID:Ethanol extract of Scutellaria baicalensis Georgi prevents oxidative damage and neuroinflammation and memorial impairments in artificial senescense mice. 2129 6

The objective of this study was to examine cell proliferation, apoptosis and angiogenesis in pathologically unchanged lung and in non-small cell lung cancer with the use of appropriate markers. The material studied included samples of pathologically unchanged lung (n=80) and those obtained at operations in 237 cases of non-small cell lung cancer. Immunohistochemical methods were used to demonstrate Ki-67, topoisomerase IIalpha (TopoIIalpha), p53, bcl-2, bax, CD34 and podoplanin. Argyrophilic proteins associated with nucleolar organizer regions (Ag-NOR proteins), were detected by impregnation with silver nitrate. The quantitative data were obtained and the peculiarities of the expression of markers associated with proliferation, apoptosis and angiogenesis in pathologically unchanged lung were determined. In the alveoli, the labeling index of Ki-67 and Topolla was less than 1%, AgNOR area index was equal to 1.31 +/- 0.20; p53, bcl-2, bax expression was absent, density of blood vessels was equal to 86 (73-102), while lymphatic vessels were absent. In the bronchus, the labeling index of Ki-67 and TopoIIalpha were respectively 4 (1-8) and less than 1%, AgNOR area index--1.85 +/- 0.24, bax expression--100%, density of blood and lymph vessels--22 (17-31) and 4 (2-7) respectively; p53 and bcl-2 expression were absent. The results were compared with the expression of markers in non-small cell lung cancer. This comparison has fundamental and differential diagnostic value in the study of histopathological lung material. The expression of markers associated with proliferation, apoptosis and angiogenesis changes from pathologically unchanged lung to non-small cell lung cancer.
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PMID:[THE PROCESSES OF CELL PROLIFERATION, APOPTOSIS AND ANGIOGENESIS IN PATHOLOGICALLY UNCHANGED LUNG AND IN NON-SMALL CELL LUNG CANCER]. 2698 21