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)

In the present study, double fluorescence staining combined with confocal laser scanning microscopy analysis were used to examine the effects of melatonin on ischemia-induced neuronal DNA strand breaks and its possible mechanisms in a transient middle cerebral artery (MCA) occlusion model. Results showed that melatonin dose-dependently reduced infarct areas and decreased both DNA double and single strand breaks (DSB and SSB) and enhanced cell viability in the peri-ischemic brain regions. Furthermore, Bcl-2 induction in the ischemic brain was further enhanced by melatonin treatment. Double staining analysis indicated that the cells costained for Bcl-2 and TdT-mediated-deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL), a DSB marker, displayed a relative regular morphology compared with the cells only stained with TUNEL. Transient ischemia induced an expression of excision repair cross-complementing factor 6 (ERCC6) mRNA, a gene essential for the preferential repair of nuclear excision repair, in the injured neurons. Double labeling showed that ERCC6 only co-localized with proliferating cell nuclear antigen (PCNA), a member of the nuclear excision repair complex, but not with TUNEL. Melatonin further and statistical significantly up-regulated ERCC6 mRNA expression in the peri-ischemic region of rat brains. The results suggest that neuroprotection by melatonin against ischemic injury may be related to modulation of apoptosis and DNA repair capacity.
J Pineal Res 2002 Aug
PMID:Neuroprotection by melatonin against ischemic neuronal injury associated with modulation of DNA damage and repair in the rat following a transient cerebral ischemia. 1212 85

In the present study, we investigated whether melatonin would prevent nitric oxide (NO)-induced apoptotic death of PGT-beta immortalized pineal cells. To examine the protective effect of melatonin, cytotoxicity assay, DNA fragmentation analysis, caspase-3 activity assay, and Western blotting for caspase-3 and poly(ADP-ribose) polymerase (PARP) were performed. Treatment of cells with S-nitroso-N-acetylpenicillamine (SNAP), an NO donor, was shown to induce apoptotic cell death in a dose-dependent manner, and pretreatment with melatonin (0.1 mm) attenuated the occurrence of NO-induced apoptotic cell death. DNA fragmentation in response to NO was also arrested by melatonin. Caspase-3 activity induced by NO was decreased with melatonin treatment. Furthermore, the active fragments of caspase-3 and PARP were almost completely absent following exposure to melatonin. To elucidate the protective mechanisms of action of melatonin, Western blot analyses for Bcl-2 expression and cytochrome c release were carried out. Pretreatment with melatonin (0.1 mm) induced the expression of Bcl-2 and suppressed the release of cytochrome c into the cytosol, thereby arresting NO-induced apoptotic cell death. These results suggest that the antiapoptotic effect of melatonin is associated with induction of Bcl-2 expression in PGT-beta cells, which in turn blocks caspase-3 activation and inhibits cytochrome c release into the cytosol.
J Pineal Res 2002 Oct
PMID:Melatonin suppresses NO-induced apoptosis via induction of Bcl-2 expression in PGT-beta immortalized pineal cells. 1222 Mar 28

Apoptosis is an important cell suicide programme involved in physiological and pathological processes. Apoptosis can be induced in different ways depending on cell type and acquired signal. Melatonin, the major secretory product of the pineal gland, participates in many important physiological functions and displays a remarkable functional versatility exhibiting antioxidant, oncostatic, anti-aging, and immunomodulatory properties. Recently, it has been shown that, in addition to pineal gland, human lymphoid cells are an important physiological source of melatonin and that may be involved in the regulation of the immune system. In this work, we examine the effect of melatonin on RAMOS-1 human leukaemic cells. Cell growth and viability, DNA fragmentation and JC-1, and annexin V expression have been determined. To elucidate the mechanism of action of melatonin, Western blot analyses for Bcl-2 and caspase-3 expression, and cytochrome c release were carried out. The results suggest that the apoptotic effect of melatonin is associated with cell-cycle arrest, downregulation of Bcl-2, mitochondrial membrane depolarization, cytochrome c release and activation of caspase-3. The intrinsic (mitochondrial dependent) pathway of caspase activation is the 'point of no return' commitment to cell death. Taken together, our study indicates that melatonin may play a role as potential therapeutic drug in specific lymphoproliferative diseases.
J Pineal Res 2005 Nov
PMID:Melatonin provokes cell death in human B-lymphoma cells by mitochondrial-dependent apoptotic pathway activation. 1620 99

The in vivo effects of melatonin on proliferation and apoptosis of 17-beta-estradiol (E2)-induced pituitary prolactin-secreting tumor (prolactinoma) were investigated in rats kept in 12 L/12 D (lights on: 06:00-18:00 hr). As melatonin was shown to induce apoptosis of breast and liver tumor cells, we examined whether melatonin would induce apoptosis of rat pituitary prolactinoma cells. 0.125, 0.25, 0.50 or 1.0 mg melatonin/day/rat was administrated subcutaneously at 17:30-18:00 hr. The weight of prolactinomas was measured. Apoptosis was evaluated using the TdT-mediated dUTP nick-end labeling method. It was found that treatment with 0.25 and 0.50 mg melatonin for 97 days inhibited prolactinoma cell proliferation and increased prolactinoma cell apoptosis. Furthermore, melatonin induced mRNA expression of Bax and cytochrome c protein expression. Conversely, mRNA expression of Bcl-2, and mitochondrial membrane potential were inhibited by melatonin treatment. These results suggest that melatonin inhibits the proliferation and induces apoptosis of rat pituitary prolactin-secreting tumor via perturbation of mitochondria physiology.
J Pineal Res 2006 Apr
PMID:Inhibitory effects of melatonin on the growth of pituitary prolactin-secreting tumor in rats. 1649 59

Oxidative stress is defined as a disturbance in the prooxidant-antioxidant balance, leading to potential cell damage. Reactive oxygen species such as superoxide radicals, hydroxyl radicals and hydrogen peroxide may act also as secondary intermediaries in intracellular signaling leading to cell death. The neuroprotective effect of melatonin has been observed both in vivo and in vitro. The objective of this research, therefore, was to better understand the cellular mechanisms of neuronal cell degeneration induced via oxidative stress and the protective roles of melatonin on this cell death. In the present study, the effects of melatonin on H(2)O(2)-induced neuronal cell degeneration in human dopaminergic neuroblastoma SH-SY5Y cultured cells were investigated. The results showed that H(2)O(2) significantly decreased cell viability and melatonin reversed the toxic effects of H(2)O(2). An inhibition of caspase enzyme activity by Ac-DEVD-CHO, a caspase-3 inhibitor, significantly increased cell viability in H(2)O(2)-treated cells. The phosphorylation of transcription factors, nuclear factor kappa B (NF-kappaB) was increased in H(2)O(2)-treated cells and this effect was abolished by melatonin. Translocation of phosphorylated NF-kappaB to perinuclear and nuclear sites, estimated using immunofluorescence, occurred to a greater extent in H(2)O(2)-treated cells than in untreated control cells and again this effect was abolished by melatonin. In addition, induction of Bcl-2 and Bax proteins was demonstrated in SH-SY5Y cultured cells treated with H(2)O(2), whereas the induction of Bax but not Bcl-2 was diminished by melatonin. In light of these finding, it is possible that the antioxidative stress effect of melatonin associated with inhibition of Bax expression, may offer a means of treating neuronal degeneration and disease.
J Pineal Res 2006 Sep
PMID:Melatonin protects against hydrogen peroxide-induced cell death signaling in SH-SY5Y cultured cells: involvement of nuclear factor kappa B, Bax and Bcl-2. 1687 16

Melatonin is the major secretory product of the pineal gland and is considered an important natural oncostatic agent. The anticancer activity of melatonin is due to its immunomodulatory, anti-proliferative and antioxidative effects. At present there are no direct data available as to melatonin's possible influence on angiogenesis, which is a major biological mechanism responsible for tumor growth and dissemination. The current study investigated the influence of melatonin on angiogenesis. Human umbilical vein endothelial cells (HUVECs) were cultured, identified, and purified. Cell growth and viability, DNA fragmentation and cell cycle analyses were determined. To elucidate the mechanism of action of melatonin, Western blot analyses for P53, Bax and Bcl-2 expression were carried out. The results demonstrate the anti-proliferative and apoptosis-inducing effects of melatonin; these changes were associated with cell cycle arrest, upregulation of P53 and Bax and downregulation of Bcl-2. Taken together, our data showed that melatonin in high concentrations markedly reduces HUVECs proliferation, induces cellular apoptosis, and modulates cell cycle length. P53 and Bax/Bcl-2 expression changes may be involved in these actions of melatonin.
J Pineal Res 2006 Nov
PMID:Effect and mechanism of melatonin's action on the proliferation of human umbilical vein endothelial cells. 1701 93

Various evidences have documented that the pineal secretory product melatonin exerts an important anti-inflammatory effect in different experimental models including colitis. The aim of the present study was to evaluate whether melatonin regulates the inflammatory response of experimental colitis in rats at the level of signal transduction pathway. Colitis was induced by intracolonic instillation of dinitrobenzene sulfonic acid (DNBS). Four days after DNBS administration, a substantial increase of colon TNF-alpha production was associated with the colon damage. In DNBS-treated rats, the colon injury correlated with a significant rise of apoptosis (evaluated by TUNEL coloration) which was associated with a significant increased expression of proapoptotic Bax and decreased colon content of antiapoptotic Bcl-2. This inflammatory response was also related to activation of nuclear factor-kappaB (NF-kappaB) and phosphorylation of c-Jun as well as FAS ligand expression in the colon. Treatment with melatonin (15 mg/kg daily i.p.) was associated with a remarkable amelioration of colonic disrupted architecture as well as a significant reduction of TNF-alpha. Melatonin also reduced the NF-kappaB activation and phosphorylation of c-Jun as well as the Fas ligand expression in the colon. Furthermore, melatonin reduced the expression of Bax and prevented the loss of Bcl-2 proteins as well as the presence of apoptotic cells caused by DNBS. The results of this study show that melatonin administration exerts beneficial effects in inflammatory bowel disease by modulating signal transduction pathways.
J Pineal Res 2006 Nov
PMID:Melatonin modulates signal transduction pathways and apoptosis in experimental colitis. 1701 94

Melatonin is an indoleamine that is synthesized in the pineal gland and has an extensive repertoire of biological activities. In the present study, we found that melatonin reduced the growth of the human myeloid leukemia cells HL-60, inhibiting progression from G(1) to S phase of the cell cycle and increasing apoptotic cell death. Furthermore, melatonin treatment elevated cytochrome c release from mitochondria and augmented caspase-3 and caspase-9 activities. Upregulation of Bax and downregulation of Bcl-2 was also observed upon melatonin treatment. The effects of melatonin were found not to be mediated by membrane receptors for the indoleamine. Together, our results suggest that melatonin reduces the viability of HL-60 cells via induction of apoptosis primarily through regulation of Bax/Bcl-2 expression.
J Pineal Res 2007 Mar
PMID:Inhibition of proliferation and induction of apoptosis by melatonin in human myeloid HL-60 cells. 1728 44

Earlier studies showed that melatonin reduced the growth of 17-beta-estradiol (E(2))-induced rat pituitary prolactin-secreting tumor (prolactinoma) in vivo. The mechanisms of melatonin's inhibitory action on the prolactin-secreting tumor were further explored by investigating the in vitro effects of melatonin on the growth of pituitary prolactin-secreting tumor cells. Primary cultured prolactinoma cells from E(2)-induced rat pituitary prolactin-secreting tumor were treated with 10(-5), 10(-4) or 10(-3) m melatonin for 5 days. Apoptosis was evaluated using flow cytometry and the TdT-mediated dUTP nick-end labeling (TUNEL) method. In addition, cell viability was analyzed by (3,4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. It was found that incubation of prolactinoma cells with 10(-5), 10(-4) or 10(-3) m melatonin for 5 days inhibited cell growth and increased cell apoptosis. Furthermore, melatonin increased caspase-3 activity, Bax mRNA expression, and cytochrome c protein expression. Conversely, Bcl-2 mRNA expression and mitochondrial membrane potential were inhibited by melatonin treatment. Our results further suggest that melatonin inhibits tumor growth by inducing apoptosis of rat pituitary prolactin-secreting tumor directly via the damage of mitochondria.
J Pineal Res 2007 Mar
PMID:Antiproliferative effects of melatonin on the growth of rat pituitary prolactin-secreting tumor cells in vitro. 1728 50

This study investigates the effects of combination therapy with melatonin and dexamethasone on the degree of spinal cord injury caused by the application of vascular clip in mice. Spinal cord injury in mice resulted in severe trauma, characterized by edema, neutrophil infiltration, and apoptosis (measured by terminal deoxynucleotidyltransferase-mediated UTP end labeling staining, and immunoreaction of Bax, Bcl-2, and Fas Ligand). Infiltration of the spinal cord tissue with neutrophils (measured as increase in myeloperoxidase activity) was associated with enhanced immuno- histochemical and functional alterations revealed, respectively, by an increased of tumor necrosis factor (TNF)-alpha immunoreactivity, NOS as well as nitrotyrosine and loss of hind leg movement in spinal cord injury (SCI)-operated mice. In contrast, the degree of neutrophil infiltration at different time points, cytokine expression, histologic damage iNOS expression, apoptosis, was markedly reduced in the tissues obtained from SCI-treated mice with the combination therapy, and the motor recovery was also ameliorated. No anti-inflammatory effect was observed in animals treated with melatonin (10 mg/kg) or with dexamethasone (0.025 mg/kg) alone. This study shows that the combination therapy with melatonin and dexamethasone reduces the degree of secondary damage associated with spinal cord injury in mice, and supports the possible use of melatonin in combination with steroids to reduce the dose and the side effects related with the use of steroids for the management of inflammatory disease.
J Pineal Res 2007 Sep
PMID:Effects of combination of melatonin and dexamethasone on secondary injury in an experimental mice model of spinal cord trauma. 1764 92


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