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)

Our aim was to examine the effects of melatonin on the testicular tissue of adult rats with experimentally-induced left varicocele, and to determine the relationship between melatonin and apoptosis regular proteins in the anti-oxidant defence system. Forty adult male Wistar rats were divided equally into four groups. A sham operation was performed on the rats in group I, and experimental left varicocele was created in groups II, III and IV. Melatonin was administered intraperitoneally at doses of 5 mg/kg and 10 mg/kg to rats in groups III and IV, respectively. An immunohistochemical analysis of the left testicular tissue was performed to evaluate the expression of Bax and Bcl-2, while tissue malondialdehyde (MDA) and antioxidant enzyme activities were assessed in homogenates to determine the role of the oxygen defence system. The immunohistochemical analysis revealed an increased ratio of pro-apoptotic protein Bax in groups II and III, whereas no significant activity was observed in the sham operated rats ( P<0.05). Similarly, the tissue MDA level increased and a significantly decreased level of antioxidant enzymes was observed in these groups ( P<0.05). Although rats in group IV showed a slightly increased ratio of the pro-apoptotic marker Bax, there was no significant difference between groups I and IV. Similarly, group IV showed decreased levels of MDA and increased levels of anti-oxidant enzyme activity with decreased Bax expression. The close relationship between pro-apoptotic/anti-apoptotic markers, reactive oxygen species and antioxidant agents provided a useful in vivo model for studying the pathophysiology of varicocele and evaluating the role of antioxidants in the prevention testicular damage.
 ...
PMID:The effects of melatonin and the antioxidant defence system on apoptosis regulator proteins (Bax and Bcl-2) in experimentally induced varicocele. 1520 54

In the present paper, we overview the discovery of new biological activities induced by ginsenoside Rg1 and Rb1 and discuss possible mechanisms of action. Both compounds could increase neural plasticity in efficacy and structure; especially Rg1, as one small molecular drug, can increase proliferation and differentiation of neural progenitor cells in dentate gyrus of hippocampus of normal adult mice and global ischemia model in gerbils. This finding has great value for treatment of Alzheimer's disease and other neurodegenerative disorders which is characterized by neurons loss. Increase of expression of brain derived neurotrophic factor, Bcl-2 and antioxidant enzyme, enhanced new synapse formation, inhibition of apoptosis and calcium overload are also important neuron protective factors. Rg1 and Rb1 have common effects, but there are some differences in pharmacology and mechanism. These differences may attribute to their different chemical structure. Rg1 is panaxtriol with two sugars, while Rb1 is panaxtriol with four sugars.
 ...
PMID:Anti-amnestic and anti-aging effects of ginsenoside Rg1 and Rb1 and its mechanism of action. 1566 89

The objective of this work was to test the hypothesis that endurance training may be protective against in vivo doxorubicin (DOX)-induced cardiomyopathy through mitochondria-mediated mechanisms. Forty adult (6-8 wk old) male Wistar rats were randomly divided into four groups (n = 10/group): nontrained, nontrained + DOX treatment (20 mg/kg), trained (14 wk of endurance treadmill running, 60-90 min/day), and trained + DOX treatment. Mitochondrial respiration, calcium tolerance, oxidative damage, heat shock proteins (HSPs), antioxidant enzyme activity, and apoptosis markers were evaluated. DOX induces mitochondrial respiratory dysfunction, oxidative damage, and histopathological lesions and triggers apoptosis (P < 0.05, n = 10). However, training limited the decrease in state 3 respiration, respiratory control ratio (RCR), uncoupled respiration, aconitase activity, and protein sulfhydryl content caused by DOX treatment and prevented the increased sensitivity to calcium in nontrained + DOX-treated rats (P < 0.05, n = 10). Moreover, training inhibited the DOX-induced increase in mitochondrial protein carbonyl groups, malondialdehyde, Bax, Bax-to-Bcl-2 ratio, and tissue caspase-3 activity (P < 0.05, n = 10). Training also increased by approximately 2-fold the expression of mitochondrial HSP-60 and tissue HSP-70 (P < 0.05, n = 10) and by approximately 1.5-fold the activity of mitochondrial and cytosolic forms of SOD (P < 0.05, n = 10). We conclude that endurance training protects heart mitochondrial respiratory function from the toxic effects of DOX, probably by improving mitochondrial and cell defense systems and reducing cell oxidative stress. In addition, endurance training limited the DOX-triggered apoptosis.
 ...
PMID:Moderate endurance training prevents doxorubicin-induced in vivo mitochondriopathy and reduces the development of cardiac apoptosis. 1579 86

Apoptosis can be evoked by reactive oxygen species (ROS)-induced mitochondrial release of the proapoptotic factors cytochrome c and apoptosis-inducing factor (AIF). Because skeletal muscle is composed of two mitochondrial subfractions that reside in distinct subcellular regions, we investigated the apoptotic susceptibility of subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria. SS and IMF mitochondria exhibited a dose-dependent release of protein in response to H2O2 (0, 25, 50, and 100 microM). However, IMF mitochondria were more sensitive to H2O2 and released a 2.5-fold and 10-fold greater amount of cytochrome c and AIF, respectively, compared with SS mitochondria. This finding coincided with a 44% (P < 0.05) greater rate of opening (maximum rate of absorbance decrease, V(max)) of the protein release channel, the mitochondrial permeability transition pore (mtPTP), in IMF mitochondria. IMF mitochondria also exhibited a 47% (P < 0.05) and 60% (0.05 < P < 0.1) greater expression of the key mtPTP component voltage-dependent anion channel and cyclophilin D, respectively, along with a threefold greater cytochrome c content, but similar levels of AIF compared with SS mitochondria. Despite a lower susceptibility to H2O2-induced release, SS mitochondria possessed a 10-fold greater Bax-to-Bcl-2 ratio (P < 0.05), a 2.7-fold greater rate of ROS production, and an approximately twofold greater membrane potential compared with IMF mitochondria. The expression of the antioxidant enzyme Mn2+-superoxide dismutase was similar between subfractions. Thus the divergent protein composition and function of the mtPTP between SS and IMF mitochondria contributes to a differential release of cytochrome c and AIF in response to ROS. Given the relatively high proportion of IMF mitochondria within a muscle fiber, this subfraction is likely most important in inducing apoptosis when presented with apoptotic stimuli, ultimately leading to myonuclear decay and muscle fiber atrophy.
 ...
PMID:Differential susceptibility of subsarcolemmal and intermyofibrillar mitochondria to apoptotic stimuli. 1590 2

Thioredoxin reductase (TrxR) in conjunction with thioredoxin (Trx) is a ubiquitous intracellular oxidoreductase system with antioxidant and redox regulatory roles. In some human tumors, the thioredoxin system is found overexpressed. We have used an antisense approach to investigate whether inhibition of TrxR overexpression can suppress the growth of human hepatocellular carcinoma SMMC-7721 cells. TrxR cDNA fragment was inserted in the antisense direction into pcDNA3.1/myc-His and SMMC-7721 cells were stably transfected with the plasmid construct. The results showed that TrxR antisense RNA could significantly reduce TrxR mRNA level and activity, and suppress the growth of SMMC-7721 cells. Cell-cycle analysis showed G2/M phase arrest in SMMC-7721 cells transfected with TrxR antisense plasmid. TrxR antisense RNA could significantly increase p53 mRNA level and decrease Bcl-2 mRNA level by reverse transcriptase-polymerase chain reaction (RT-PCR). Furthermore a significant decrease in human telomerase reverse transcriptase (hTERT) mRNA level was found in SMMC-7721 cells transfected with TrxR antisense plasmid. Flow cytometry and telomere fluorescence in situ hybridization (Flow FISH) showed that TrxR antisense RNA could significantly reduce the telomere fluorescence in SMMC-7721 cells. The results suggested that TrxR antisene RNA inhibited the growth of SMMC-7721 cells through an accumulation of cell cycle at G2/M phase, an increase in p53 mRNA level and a reduction in telomere fluorescence and Bcl-2, hTERT mRNA levels.
 ...
PMID:Inhibitory effects of thioredoxin reductase antisense RNA on the growth of human hepatocellular carcinoma cells. 1608 46

The transcription factor nuclear factor kappa-B (NF-kappaB) is involved in regulating responses of neurons to activation of several different signaling pathways in a variety of physiological and pathological settings. During development of the nervous system NF-kappaB is activated in growing neurons by neurotrophic factors and can induce the expression of genes involved in cell differentiation and survival. In the mature nervous system NF-kappaB is activated in synapses in response to excitatory synaptic transmission and may play a pivotal role in processes such as learning and memory. NF-kappaB is activated in neurons and glial cells in acute neurodegenerative conditions such as stroke and traumatic injury, as well as in chronic neurodegenerative conditions such as Alzheimer's disease. Activation of NF-kappaB in neurons can promote their survival by inducing the expression of genes encoding anti-apoptotic proteins such as Bcl-2 and the antioxidant enzyme Mn-superoxide dismutase. On the other hand, by inducing the production and release of inflammatory cytokines, reactive oxygen molecules and excitotoxins, activation of NF-kappaB in microglia and astrocytes may contribute to neuronal degeneration. Emerging findings suggest roles for NF-kappaB as a mediator of effects of behavioral and dietary factors on neuronal plasticity. NF-kappaB provides an attractive target for the development of novel therapeutic approaches for a range of neurological disorders.
 ...
PMID:NF-kappaB in the survival and plasticity of neurons. 1618 23

Radix Angelica sinensis, known as Danggui in Chinese, has been used to treat cardiovascular and cerebrovascular diseases in Traditional Chinese Medicine for a long time. Modern phytochemical studies showed that Z-ligustilide (LIG) is the main lipophilic component of Danggui. In this study, we examined whether LIG could protect ischemia/reperfusion-induced brain injury by minimizing oxidative stress and anti-apoptosis. Transient forebrain cerebral ischemia (FCI) was induced by the bilateral common carotid arteries occlusion for 30 min. LIG was intraperitoneally injected to ICR mice at the beginning of reperfusion. As determined via 2,3,5-triphenyl tetrazolium chloride (TTC) staining at 24 h following ischemia, the infarction volume in the FCI mice treated without LIG (22.1 +/- 2.6%) was significantly higher than that in the FCI mice treated with 5 mg/kg (11.8 +/- 5.2%) and 20 mg/kg (2.60 +/- 1.5%) LIG (P < 0.05 or P < 0.01). LIG treatment significantly decreased the level of malondialdehyde (MDA) and increased the activities of the antioxidant enzyme glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) in the ischemic brain tissues (P < 0.05 or P < 0.01 vs. FCI group). In addition, LIG provided a great increase in Bcl-2 expression as well as a significant decrease in Bax and caspase-3 immunoreactivities in the ischemic cortex. The findings demonstrated that LIG could significantly protect the brain from damage induced by transient forebrain cerebral ischemia. The antioxidant and anti-apoptotic properties of LIG may contribute to the neuroprotective potential of LIG in cerebral ischemic damage.
 ...
PMID:Neuroprotective role of Z-ligustilide against forebrain ischemic injury in ICR mice. 1680 12

Oxidative stress, including the generation of reactive oxygen species (ROS), is known to be involved in apoptosis. Preventing apoptosis may thereby induce a malignant transformation of liver tumor cells. Estradiol (E2) is a potent endogenous antioxidant. We examined the proapoptotic role of progesterone as well as the antiapoptotic role of E2 in human hepatoma HuH-7 cells in a state of early apoptosis induced by tumor necrosis factor (TNF) alpha. The TNF alpha-induced ROS generation, lipid peroxidation, antioxidant enzyme consumption, a proapoptotic predominant expression of Bcl-2 family proteins, and a disruption of mitochondrial membrane potential were all inhibited by E2, and then they were further stimulated by progesterone in HuH-7 cells. The inhibitory effects of E2 were blocked by coincubation with progesterone. Treatment with the progesterone receptor antagonist RU486 led to the blockage of the progesterone-mediated responses to E2 pretreatment in TNF alpha-induced apoptosis. These findings demonstrate that E2 inhibits the TNF alpha-induced early apoptosis in hepatoma cells, by suppressing the oxidative stress processes, whereas progesterone acts in a manner opposite from the effects of E2, and the inhibitory effects of E2 were blocked by progesterone, thus leading to the apoptosis of hepatoma cells.
 ...
PMID:Effects of estradiol and progesterone on tumor necrosis factor alpha-induced apoptosis in human hepatoma HuH-7 cells. 1686 Aug 28

This review focuses on evidence that oxidative stress during apoptosis is controlled, at least in part, by modulating cellular antioxidant defences. Evidence is presented from studies of apoptosis induced by glucocorticoids, HIV-1 infection and tumour necrosis factor-alpha. Glucocorticoid treatment of murine lymphocyte cell lines leads to the down-regulation of primary antioxidant defence enzymes, including catalase, superoxide dismutases, thioredoxin and DT-diaphorase. Following HIV-1 infection, disturbances in glutathione metabolism are seen, and decreased antioxidant enzyme activities have been reported for HIV-1-infected cell lines. The viral protein Tat may mediate these effects. Cellular resistance to apoptosis induced by tumour necrosis factor-alpha is modulated by the expression of manganese superoxide dismutase or Bcl-2. The loss of antioxidant defences is predicted to lead to oxidative stress, which could contribute to the mechanism of apoptosis through an effect on redox-sensitive transcription factors, calcium homeostasis or cysteine proteases.
 ...
PMID:Modulation of the antioxidant defence as a factor in apoptosis. 1718 56

Lupeol, a triterpene present in mango and other fruits, is known to exhibit a number of pharmacological properties including antioxidant, antilithiatic, and antidiabetic effects. In the present study, chemopreventive properties of lupeol and mango pulp extract (MPE) were evaluated against 7,12-dimethylbenz(a)anthracene (DMBA) induced alteration in liver of Swiss albino mice. Lupeol (25 mg/kg body weight, bw) or 1 mL of 20% w/v aqueous MPE/mouse were daily given once for 1 wk after a single dose of DMBA (50 mg/kg bw). Lupeol/MPE supplementation effectively influenced the DMBA induced oxidative stress, characterized by restored antioxidant enzyme activities and decrease in lipid peroxidation. A reduction of apoptotic cell population in the hypodiploid region was observed in lupeol and MPE supplemented animals. The inhibition of apoptosis was preceded by decrease in reactive oxygen species (ROS) level and restoration of mitochondrial transmembrane potential followed by decreased DNA fragmentation. In DMBA treated animals, downregulation of antiapoptotic Bcl-2 and upregulation of proapoptotic Bax and Caspase 3 in mouse liver was observed. These alterations were restored by lupeol/MPE, indicating inhibition of apoptosis. Thus, lupeol/MPE was found to be effective in combating oxidative stress induced cellular injury of mouse liver by modulating cell-growth regulators.
 ...
PMID:Hepatoprotective effects of lupeol and mango pulp extract of carcinogen induced alteration in Swiss albino mice. 1734 May 78


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>