Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:P10415 (Bcl-2)
33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cultured cells are able to oxidize low-density lipoproteins (LDL) and oxidized LDL (oxLDL), which are present in atherosclerosis areas, exhibit a variety of biological properties potentially involved in atherogenesis. This review is focused on the toxicity of oxLDL, more precisely on the toxic compounds generated during LDL oxidation, the features and the mechanisms of cell death (apoptosis or necrosis) induced by oxLDL. After internalization, toxic oxidized lipids, namely lipid peroxides, oxysterols and aldehydes, induce modifications of cell proteins, elicit oxidative stress, lipid peroxidation and alter various signaling pathways and gene expression. These events may participate in the toxic effect, and converge to trigger an intense, delayed and sustained calcium peak which elicits either apoptosis or necrosis processes. OxLDL-induced apoptosis involves both mitochondrial and death-receptor (Fas/FasL) apoptotic pathways, thereby activating the classical caspase cascade and subsequent biochemical and morphological apoptotic features. When apoptosis is blocked by overexpression of Bcl-2, oxLDL trigger necrosis through a calcium-dependent pathway. Apoptosis occurring in atherosclerotic areas is potentially involved in endothelial cell lining defects, necrotic core formation and plaque rupture or erosion which may trigger atherothrombotic events. However, the precise role of oxLDL in apoptosis/necrosis occurring in vivo in atherosclerotic plaques remains to be clarified.
...
PMID:Oxidized low-density lipoprotein-induced apoptosis. 1253 56

A plethora of studies in cultured cells have established that oxidized low-density lipoprotein (oxLDL) may enhance arterial apoptosis that involves both mitochondrial and death receptor pathways (Fas/FasL, TNF receptors I and II), thereby activating caspase cascade and other proteases. When apoptosis is inhibited by Bcl-2 overexpression, oxLDL may trigger necrosis through a calcium-dependent pathway. Despite this effort, the pathophysiological relevance of apoptosis in vivo remains to be elucidated. In principle, apoptosis occurring in atherosclerotic areas could be involved in endothelial cell lining defects, necrotic core formation, and plaque rupture or fissuring. This complex pathogenic framework may favor coronary atherothrombotic events. To date, the pathogenic role of apoptosis in thrombosis is attractive, but a solid evidence is still needed. When the precise role of oxLDL in vascular programmed cell death occurring in vivo is clarified, this may aid in the development of novel therapeutic approaches to adverse atherogenesis and its clinical sequelae.
...
PMID:Oxidation of LDL, atherogenesis, and apoptosis. 1503 14

We measured the mRNA expression levels of molecules involved in scavenging free radicals and in apoptosis within normal appearing white and gray matter (NAWM and NAGM, respectively) and chronic active plaque containing frontal lobe specimens of patients with multiple sclerosis (MS). While no regional differences were detected in the mRNA levels of free radical scavengers, Bcl-XL was higher in plaques than in NAWMs, and both Bak and Bcl-2 were found to be increased in correlation with an immune marker (beta2-microglobulin--beta2Mg) in NAWM and plaque compared with corresponding cortical regions. We did not measure a similar white-gray matter difference in the expression of the latter genes in brains of normal or Alzheimer disease controls. This finding indicates that both pro- and anti-apoptotic mechanisms are activated, not only within but also outside of plaques.
...
PMID:Bcl-2 and its homologues in the brain of patients with multiple sclerosis. 1512 64

Today, implant-supported prostheses are widely accepted as a reliable treatment modality, but failures in longitudinal studies have been shown. In some cases, peri-implantitis with a progressive periodontal bone loss takes place, and mechanical or load factors and biological or plaque-induced lesions have been claimed as main etiologic factors. We compared five cases of peri-implantitis, with five cases of healthy peri-implant tissues and five cases of aggressive periodontitis in order to give new findings on the osseointegration loss process. Biopsy specimens from the peri-implant tissues including oral (O), sulcular, and junctional epithelium and the underlying and supracrestal connective tissue, were taken in all cases for histological and immunohistochemical analysis. T lymphocytes were the most prominent cell in the peri-implantitis (PG) and aggressive periodontitis (AG) groups, but not in the peri-implant healthy group (HG). CD1a-positive cells (Langerhans and immature dendritic cells) were observed more frequently in the O than in the sulcular-junctional (S-J) epithelium: they were located in the basal and parabasal layers, without any differences between the three groups. Vascular proliferation analysed by immunoreactivity for CD34, Factor VIII, and vascular endothelial growth factor was more prominent in the PG comparing with HG and AG in the S-J area. Apoptosis, analysed by bcl2 and p53 immunoreactivity, was similar in the three groups. In conclusion, we suggest that the osseointegration loss process is due to an inflammatory process similar to that observed in aggressive periodontitis according to the number of T lymphocytes, but not to the vascular proliferation.
...
PMID:Immunohistochemical analysis of soft tissues in implants with healthy and peri-implantitis condition, and aggressive periodontitis. 1535 97

Atherosclerotic plaque contains apoptotic endothelial cells with oxidative stress implicated in this process. Vitamin E and alpha-lipoic acid are a potent antioxidant combination with the potential to prevent endothelial apoptosis. Regular exercise is known to increase myocardial protection, however, little research has investigated the effects of exercise on the endothelium. The purpose of these studies was to investigate the effects of antioxidant supplementation and/or exercise training on proteins that regulate apoptosis in endothelial cells. Male rats received a control or antioxidant-supplemented diet (vitamin E and alpha-lipoic acid) and were assigned to sedentary or exercise-trained groups for 14 weeks. Left ventricular endothelial cells (LVECs) were isolated and levels of the anti-apoptotic protein Bcl-2 and the pro-apoptotic protein Bax were measured. Antioxidant supplementation caused a fourfold increase in Bcl-2 (P < 0.05) with no change in Bax (P > 0.05). Bcl-2:Bax was increased sixfold with antioxidant supplementation compared to non-supplemented animals (P < 0.05). Exercise training had no significant effect on Bcl-2, Bax or Bcl-2:Bax either alone or combined with antioxidant supplementation (P > 0.05) compared to non-supplemented animals. However, Bax was significantly lower (P < 0.05) in the supplemented trained group compared to non-supplemented trained animals. Cultured bovine endothelial cells incubated for 24 h with vitamin E and/or alpha-lipoic acid showed the combination of the two antioxidants increased Bcl-2 to a greater extent than cells incubated with the vehicle alone. In summary, vitamin E and alpha-lipoic acid increase endothelial cell Bcl-2, which may provide increased protection against apoptosis.
...
PMID:Bcl-2 in endothelial cells is increased by vitamin E and alpha-lipoic acid supplementation but not exercise training. 1573 4

The aim of this study was to investigate the differences that are present between apoptosis in symptomatic (with symptoms of cerebral ischemic attack) and asymptomatic carotid atherosclerotic plaques. The apoptotic process in macrophages and smooth muscle cells was evaluated. Cellular markers and products of immune cells in symptomatic and asymptomatic atherosclerotic plaque and endoarterectomy specimen were analyzed by immunohistochemistry. No statistically significant differences were present regarding the mean SMC actin-positive area. Using double staining of alpha-smooth muscle actin and TUNEL techniques, the number of smooth muscle cells in apoptosis was statistically higher in symptomatic plaque as compared with asymptomatic plaque. Statistically significant differences (p=0.009) were also found in the CD45-positive cells in the inflammatory infiltrate. The CD68-positive macrophages showed statistically significant differences (p=0.0001). Similarly, the double staining with CD68 and TUNEL revealed that apoptotic macrophages were mainly present in asymptomatic plaques rather than symptomatic plaques. Statistically significant differences (p<0.001) were found in the Bcl-2 expression, with higher values in asymptomatic plaques. Our data showed that the increase of the inflammatory cells contributes to plaque instability and that death due to apoptosis of smooth muscle cells in symptomatic plaques could contribute to their destabilization and explains their tendency to fracture.
...
PMID:Factors associated with apoptosis in symptomatic and asymptomatic carotid atherosclerotic plaques. 1638 11

Tioman virus is a newly described bat-urine derived paramyxovirus isolated in Tioman Island, Malaysia in 2001. Hitherto, neither human nor animal infection by this virus has been reported. Nonetheless, its close relationship to another paramyxovirus, the Menangle virus which had caused diseases in humans and pigs [Philbey, A.W., Kirkland, P.D., Ross, A.D., Davis, R.J., Gleeson, A.B., Love, R.J., Daniels, P.W., Gould, A.R., Hyatt, A.D., 1998. An apparently new virus (family Paramyxoviridae) infectious for pigs, humans, and fruit bats. Emerg. Infect. Dis. 4, 269-271], raises the possibility that it may be potentially pathogenic. In this study, mice were experimentally infected with Tioman virus by intraperitoneal and intracerebral routes, and the cellular targets and topographical distribution of viral genome and antigens were examined using in situ hybridization and immunohistochemistry, respectively. The possible association between viral infection and apoptosis was also investigated using the TUNEL assay and immunohistochemistry to FasL, Caspase-3, Caspase-8, Caspase-9 and bcl-2. The results showed that Tioman virus inoculated intracerebrally was neurotropic causing plaque-like necrotic areas, and appeared to preferentially replicate in the neocortex and limbic system. Viral infection of inflammatory cells was also demonstrated. TUNEL and Caspase-3 positivity was found in inflammatory cells but not in neurons, while FasL, Caspase-8 and Caspase-9 were consistently negative. This suggests that neuronal infection was associated with necrosis rather than apoptosis. Moreover, the data suggest that there may be an association between viral infection and apoptosis in inflammatory cells, and that it could, at least in part, involve Caspase-independent pathways. Bcl-2 was expressed in some neurons and inflammatory cells indicating its possible role in anti-apoptosis. There was no evidence of central nervous system infection via the intraperitoneal route.
...
PMID:Tioman virus infection in experimentally infected mouse brain and its association with apoptosis. 1744 9

In view of the powerful inherent oncolytic activity exhibited by the vesicular stomatitis virus (VSV) in several tumor types, we set out to investigate the susceptibility of the immortalized HaCaT keratinocyte cell line to VSV, and analyzed the role of apoptosis in the VSV-mediated induction of cell death. Indirect immunofluorescence assays, Western blot analyses and plaque titrations demonstrated that the HaCaT cell line was permissive to VSV replication. The results of ELISA for detection of the enrichment of nucleosomes in the cytoplasm of apoptotic cells revealed that VSV infection elicits the apoptotic death of HaCaT cells. Mock-infected HaCaT cells displayed the endogenous expression of DeltaNp63alpha, p53 mutated on UV hot spots (p53(mt)), Bcl-2 and p21 Bax. The levels of DeltaNp63alpha and p53(mt) were decreased, Bcl-2 remained unaffected, while the expressions of p21Bax and p18 Bax were increased in VSV-infected HaCaT cells. Together, these data demonstrate that VSV replicates efficiently and triggers apoptosis in the immortalized HaCaT keratinocyte cell line. The VSV-mediated alterations in the expressions of DeltaNp63alpha and Bax may be implicated in the apoptotic responses of infected cells and may also sensitize to other apoptotic stimuli. These findings may stimulate further studies with the goal of developing VSV-based virotherapy into an effective modality for the treatment of epithelial-derived malignant tumors of the skin.
...
PMID:Vesicular stomatitis virus infection triggers apoptosis associated with decreased DeltaNp63alpha and increased Bax levels in the immortalized HaCaT keratinocyte cell line. 1745 50

The inappropriate survival of cells in the neointima contributes to atherosclerotic plaque progression, while apoptosis in the fibrous cap of lesions contributes to myocardial infarction and stroke. Prior genomic-scale transcript profiling of human carotid artery plaque cells with known sensitivity or resistance to fas-induced apoptosis identified candidate genes involved in lesion cell apoptosis. Retroviral overexpression indicated that several candidate factors were not causative, but that Bcl-X(L) conferred complete resistance to apoptosis induced by fas ligation. Resistant cells failed to efficiently activate caspase 8, an effect which was also observed in Bcl-X(L)-transfected cells. Small-molecule Bcl-2/X(L) inhibitors and siRNA knockdown of Bcl-X(L) markedly sensitized resistant cells to apoptosis, and partially restored caspase 8 activation. Caspase 3, 6 and 9 inhibitors reduced caspase 8 activation and blocked apoptosis. Complete knockdown of caspase 9 did not reduce apoptosis, while knockdown of Bid suppressed apoptosis, suggesting that mitochondrial pathways independent of caspase 9, such as Smac/Diablo or AIF, provide a necessary mitochondrial input to efficient caspase activation. Bcl-X(L) appears to modulate lesion cell apoptosis by suppressing mitochondrial amplification of caspase activation loops. The results may have direct implications for controlling plaque instability/progression, and identify a new class of small molecules to inhibit restenosis.
...
PMID:Resistance to fas-induced apoptosis in cells from human atherosclerotic lesions: elevated Bcl-XL inhibits apoptosis and caspase activation. 1765 64

Alzheimer's disease (AD) is a terminal age-associated dementia characterized by early synaptic dysfunction and late neurodegeneration. Although the presence of plaques of fibrillar aggregates of the amyloid beta peptide (Abeta) is a signature of AD, evidence suggests that the preplaque small oligomeric Abeta promotes both synaptic dysfunction and neuronal death. We found that young Tg2576 transgenic mice, which accumulate Abeta and develop cognitive impairments prior to plaque deposition, have high central nervous system (CNS) activity of calcineurin (CaN), a phosphatase involved in negative regulation of memory function via inactivation of the transcription factor cAMP responsive element binding proteins (CREB), and display CaN-dependent memory deficits. These results thus suggested the involvement of prefibrillary forms of Abeta. To investigate this issue, we compared the effect of monomeric, oligomeric, and fibrillar Abeta on CaN activity, CaN-dependent pCREB and phosphorylated Bcl-2 Associated death Protein (pBAD) levels, and cell death in SY5Y cells and in rat brain slices, and determined the role of CaN on CREB phosphorylation in the CNS of Tg2576 mice. Our results show that oligomeric Abeta specifically induces CaN activity and promotes CaN-dependent CREB and Bcl-2 Asociated death Protein (BAD) dephosphorylation and cell death. Furthermore, Tg2576 mice display Abeta oligomers and reduced pCREB in the CNS, which is normalized by CaN inhibition. These findings suggest a role for CaN in mediating effects of oligomeric Abeta on neural cells. Because elevated CaN levels have been reported in the CNS of cognitively impaired aged rodents, our results further suggest that abnormal CaN hyperactivity may be a common event exacerbating the cognitive and neurodegenerative impact of oligomeric Abeta in the aging CNS.
...
PMID:Selective induction of calcineurin activity and signaling by oligomeric amyloid beta. 1878 50


<< Previous 1 2 3 4 5 6 7 Next >>

---