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)

The aim of this study was to investigate the anti-tumor effects and mechanism of the selenium heteropoly compound (C(2)H(10)N(2))(5)(NH(4))(4)H(2)[Se(2)W(10)V(8)O(62)].9H(2)O (SeWV) in K562 cells. The results showed that 0.32-10.15 x 10(-3) mmol/l SeWV could significantly inhibit the proliferation of K562 cells in vitro, as determined by the MTT assay, with IC(50) values of 3.07 and 2.69 x 10(-3) mmol/l after 48 and 72 h of treatment with SeWV, respectively. Studies of the cell cycle indicated that SeWV could induce K562 cells gathered in the G(2)/M phase upon treatment for 24 and 48 h, and a significant sub-G1 peak was evident at 0.32 and 2.54 x 10(-3) mmol/l after treatment for 24 h. Morphological observations revealed typical apoptotic features. SeWV caused the accumulation of Ca(2+), Mg(2+) and ROS, and the reduction of pH and mitochondrial membrane potential (MMP) in K562 cells as evidenced by confocal laser scanning microscopy. Experiments also showed that the expression of Bcl-2 was significantly inhibited, but Bax was increased by SeWVat 5.07 x 10(-3) mmol/l. Additionally, the content of cytochrome-C was increased after treatment for 24 h. The experiment implied that SeWV had anti-tumor activity and that its mechanism was partially attributable to the induction of cell cycle distribution and apoptosis that was induced by a change in intracellular ion homeostasis.
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PMID:Antitumor effects of a selenium heteropoly complex in K562 cells. 1944 41

Xyloketal B is a novel marine compound with unique chemical structure isolated from mangrove fungus Xylaria sp. (no. 2508). Pretreatment with xyloketal B (0.63-40 microM) significantly improved oxLDL (150 microg/ml)-induced injury in human umbilical vein endothelial cells (HUVECs) without either toxic or proliferative effects. Xyloketal B concentration-dependently attenuated oxLDL-induced ROS generation, peroxynitrite formation and decrease of Bcl-2 expression. In addition, xyloketal B significantly inhibited NADPH oxidase activity, as well as mRNA expression of gp91phox and p47phox. Furthermore, xyloketal B alone augmented the production of nitric oxide (NO). Collectively, these data indicate that xyloketal B protects against oxLDL-induced endothelial oxidative injury probably through inhibiting NADPH oxidase-derived ROS generation, promoting NO production and restoring Bcl-2 expression, making it a promising compound for further evaluation in the treatment of atherosclerosis.
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PMID:A novel marine compound xyloketal B protects against oxidized LDL-induced cell injury in vitro. 1948 Oct 65

Bcl-2 is recognized as an oncoprotein via its ability to impede death signaling by sequestrating pro-apoptotic proteins such as Bax and Bak as well as preserving mitochondrial outer membrane integrity. Recently, a growing body of evidence has evaluated the role of Bcl-2 in intracellular redox regulation and its downstream effects on life and death decisions in cancer cells. On the backdrop of these findings, we discuss here the classical anti-apoptotic role of Bcl-2 in malignant cells, and review the significance of Bcl-2-mediated regulation of tumor redox status. We discuss recent evidence that underscores a paradigm shift in the way cellular redox status impacts cell fate decisions via the effect of Bcl-2 on mitochondrial physiology. The ability of Bcl-2 to promote, modulate and optimize mitochondrial respiration under different redox states highlights the importance of mitochondrial bioenergetics, ROS and the roles they might play in the onset and/or maintenance of oncogenesis.
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PMID:BCL-2: pro-or anti-oxidant? 1948 43

Limitation of infarct size by ischemic/pharmacological pre- and postconditioning involves activation of a complex set of cell-signaling pathways. Multiple lines of evidence implicate the mitochondrial permeability transition pore (mPTP) as a key end effector of ischemic/pharmacological pre- and postconditioning. Increasing the ROS threshold for mPTP induction enhances the resistance of cardiomyocytes to oxidant stress and results in infarct size reduction. Here, we survey and synthesize the present knowledge about the role of glycogen synthase kinase (GSK)-3beta in cardioprotection, including pre- and postconditioning. Activation of a wide spectrum of cardioprotective signaling pathways is associated with phosphorylation and inhibition of a discrete pool of GSK-3beta relevant to mitochondrial signaling. Therefore, GSK-3beta has emerged as the integration point of many of these pathways and plays a central role in transferring protective signals downstream to target(s) that act at or in proximity to the mPTP. Bcl-2 family proteins and mPTP-regulatory elements, such as adenine nucleotide translocator and cyclophilin D (possibly voltage-dependent anion channel), may be the functional downstream target(s) of GSK-3beta. Gaining a better understanding of these interactions to control and prevent mPTP induction when appropriate will enable us to decrease the negative impact of the reperfusion-induced ROS burst on the fate of mitochondria and perhaps allow us to limit propagation of damage throughout and between cells and consequently, to better limit infarct size.
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PMID:Role of glycogen synthase kinase-3beta in cardioprotection. 1949 10

In this study, the protective effects of water extracts from pine needle (WEPN) against DNA damage and apoptosis induced by hydroxyl radical were investigated in non-cellular and cellular system. WEPN exhibited strong scavenging action on hydroxyl radical and intracellular ROS, and chelating action of Fe(2+) ion. WEPN inhibited oxidative DNA damage by hydroxyl radical. Also, WEPN prevented the cells from oxidative damage through lowering p21 and BAX protein expression, blocking the cleavage of PARP and increasing Bcl-2 protein, which was confirmed by Hoechst 33342 staining. These data indicate that WEPN possesses a spectrum of antioxidant and DNA-protective properties common to cancer chemopreventive agents.
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PMID:Effect of extracts from pine needle against oxidative DNA damage and apoptosis induced by hydroxyl radical via antioxidant activity. 1950 Jun 37

Neurons are highly dependent on astrocyte survival during brain damage. To identify genes involved in astrocyte function during ischemia, we performed mRNA differential display in astrocytes after oxygen and glucose deprivation (OGD). We detected a robust down-regulation of S6 kinase 1 (S6K1) mRNA that was accompanied by a sharp decrease in protein levels and activity. OGD-induced apoptosis was increased by the combined deletion of S6K1 and S6K2 genes, as well as by treatment with rapamycin that inhibits S6K1 activity by acting on the upstream regulator mTOR (mammalian target of rapamycin). Astrocytes lacking S6K1 and S6K2 (S6K1;S6K2-/-) displayed a defect in BAD phosphorylation and in the expression of the anti-apoptotic factors Bcl-2 and Bcl-xL. Furthermore reactive oxygen species were increased while translation recovery was impaired in S6K-deficient astrocytes following OGD. Rescue of either S6K1 or S6K2 expression by adenoviral infection revealed that protective functions were specifically mediated by S6K1, because this isoform selectively promoted resistance to OGD and reduction of ROS levels. Finally, "in vivo" effects of S6K suppression were analyzed in the permanent middle cerebral artery occlusion model of ischemia, in which absence of S6K expression increased mortality and infarct volume. In summary, this article uncovers a protective role for astrocyte S6K1 against brain ischemia, indicating a functional pathway that senses nutrient and oxygen levels and may be beneficial for neuronal survival.
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PMID:mTOR/S6 kinase pathway contributes to astrocyte survival during ischemia. 1953 30

Arachidonic acid (AA)-induced apoptosis of human neuroblastoma SK-N-SH cells was characteristic of elevation of intracellular Ca(2+) concentration ([Ca(2+)]i), ROS generation, activation of 38 MAPK and JNK and loss of mitochondrial membrane potential (DeltaPsim). Subsequent modulation of Bcl-2 family members and cytochrome c release accompanied with activation of caspase-9 and -3 were involved in the death of SK-N-SH cells. BAPTA-AM (Ca(2+) chelator) pretreatment rescued viability of AA-treated cells through abolishing phosphorylation of p38 MAPK and JNK, DeltaPsim loss and ROS generation. N-Acetylcysteine (ROS scavenger) pretreatment reduced the dissipation of DeltaPsim, but insignificantly affected AA-induced p38 MAPK and JNK activation. SB202190 (p38 MAPK inhibitor) and SP600125 (JNK inhibitor) attenuated mitochondrial depolarization, degradation of Bcl-2/Bcl-xL, and mitochondrial translocation of Bax. Transfection of specific siRNA proved that p38alpha MAPK and JNK1 were involved in modulating Bcl-2 family proteins. Taken together, our data suggest that the cytotoxicity of AA toward SK-N-SH cells is mediated through mitochondria-dependent death pathway, eliciting by AA-induced ROS generation and Ca(2+)-evoked activation of p38alpha MAPK and JNK1.
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PMID:Arachidonic acid-induced apoptosis of human neuroblastoma SK-N-SH cells is mediated through mitochondrial alteration elicited by ROS and Ca(2+)-evoked activation of p38alpha MAPK and JNK1. 1954 Sep 2

Our previous study has shown that sodium selenite can cause apoptosis in acute promyelocytic leukemia-derived NB4 cells in a caspase-dependent manner involving Deltapsim disruption and cleavage of Bcl-2, but more detailed mechanism(s) remain unclear. Here we showed that mitochondrial apoptosis signaling pathway played a vital role in apoptosis induced by sodium selenite based on the following findings: 1) cytochrome c release, activation of caspase 9, mitochondrial targeting, and oligermerization of Bax; 2) caspase 9, but not caspase 8, inhibitor could attenuate apoptosis; 3) downregulation of Bax and Bad by siRNA could delay sodium selenite-induced apoptosis. Further investigation showed that ROS was an essential inducer of deltapsim disruption and apoptosis by sodium selenite. Our findings here demonstrate that sodium selenite can induce apoptosis in NB4 cells through a mechanism involving ROS, activation of proapoptotic proteins Bad and Bax, Deltapsim disruption, release of cytochrome c, and consequent initiation of caspase cascade.
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PMID:Sodium selenite induces apoptosis in acute promyelocytic leukemia-derived NB4 cells through mitochondria-dependent pathway. 1954 74

The present study has been designed and carried out to investigate the protective role of taurine (2-aminoethanesulphonic acid) against NaAsO(2) induced nephrotoxicity. Oral administration of arsenic increased the productions of ROS and RNS, enhanced lipid peroxidation, protein carbonylation and decreased intracellular antioxidant defence in the kidney tissue. Investigating the responsible signalling cascades, it was found that NaAsO(2) administration activates mitogen-activated protein kinases (MAPKs) and NF-kappaB in oxidative stress mediated renal dysfunction and induced apoptotic cell death by the reciprocal regulation of Bcl-2/Bad in association with reducing mitochondrial membrane potential and increased cytosolic cytochrome C as well. Treatment with taurine prior to arsenic administration effectively ameliorated As-induced oxidative renal dysfunctions and apoptotic cell death. Histological studies also support the experimental findings. Combining, results suggest that taurine possesses the ability to ameliorate arsenic-induced oxidative insult and renal damage, probably due to its antioxidant activity and functioning via MAPKs/NF-kappaB and mitochondria dependent pathways.
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PMID:Prophylactic role of taurine on arsenic mediated oxidative renal dysfunction via MAPKs/ NF-kappaB and mitochondria dependent pathways. 1967 40

The infiltration and persistence of hematopoietic immune cells within the rheumatoid arthritis (RA) joint results in elevated levels of pro-inflammatory cytokines, increased reactive oxygen (ROS) and -nitrogen (RNS) species generation, that feeds a continuous self-perpetuating cycle of inflammation and destruction. Meanwhile, the controlled production of ROS is required for signaling within the normal physiological reaction to perceived "foreign matter" and for effective apoptosis. This review focuses on the signaling pathways responsible for the induction of the normal immune response and the contribution of ROS to this process. Evidence for defects in the ability of immune cells in RA to regulate the generation of ROS and the consequence for their immune function and for RA progression is considered. As the hypercellularity of the rheumatoid joint and the associated persistence of hematopoietic cells within the rheumatoid joint are symptomatic of unresponsiveness to apoptotic stimuli, the role of apoptotic signaling proteins (specifically Bcl-2 family members and the tumor suppressor p53) as regulators of ROS generation and apoptosis are considered, evaluating evidence for their aberrant expression and function in RA. We postulate that ROS generation is required for effective therapeutic intervention.
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PMID:Aberrant reactive oxygen and nitrogen species generation in rheumatoid arthritis (RA): causes and consequences for immune function, cell survival, and therapeutic intervention. 1968 39


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