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21.
Modulation of ROS/MAPK signaling pathways by okadaic acid leads to cell death via,mitochondrial mediated caspase-dependent mechanism 总被引:1,自引:0,他引:1
Ravindran J Gupta N Agrawal M Bala Bhaskar AS Lakshmana Rao PV 《Apoptosis : an international journal on programmed cell death》2011,16(2):145-161
Okadaic acid (OA) is a specific and potent protein phosphatase inhibitor and tumor promoter. The present study establishes the role of reactive oxygen species (ROS) and mitogen activated protein kinases in cell death induced by okadaic acid. The study showed that okadaic acid is cytotoxic at 10 nM with an IC50 of 100 nM in U-937 cells. The CVDE assay and mitochondrial dehydrogenase assay showed a time dependent cytotoxicity. The phase contrast visualization of the OA treated cells showed the apoptotic morphology and was confirmed with esterase staining for plasma membrane integrity. OA activated caspases-7, 9 and 3, PARP cleavage and induced nuclear damage in a time and dose dependent manner. Compromised mitochondrial membrane potential, release of cytochrome-c and apoptosis inducing factor confirms the involvement of mitochondria. A time dependent decrease in glutathione levels and a dose dependent increase in ROS with maximum at 30 min were observed. ROS scavenger-N-acetyl cysteine, mitochondrial stabilizer-cyclosporin-A, and broad spectrum caspase inhibitor Z-VAD-FMK inhibited the OA induced caspase-3 activation, DNA damage and cell death but caspase-8 inhibitor had no effect. OA activated p38 MAPK and JNK in a time dependent manner, but not ERK½. MAP kinase inhibitors SB203580, SP600125 and PD98059 confirm the role of p38 MAPK and JNK in OA induced caspase-3 activation and cell death. Over all, our results indicate that OA induces cell death by generation of ROS, and activation of p38 MAPK and JNK, and executed through mitochondrial mediated caspase pathway. 相似文献
22.
Cadmium stress: an oxidative challenge 总被引:5,自引:0,他引:5
Ann Cuypers Michelle Plusquin Tony Remans Marijke Jozefczak Els Keunen Heidi Gielen Kelly Opdenakker Ambily Ravindran Nair Elke Munters Tom J. Artois Tim Nawrot Jaco Vangronsveld Karen Smeets 《Biometals》2010,23(5):927-940
At the cellular level, cadmium (Cd) induces both damaging and repair processes in which the cellular redox status plays a crucial role. Being not redox-active, Cd is unable to generate reactive oxygen species (ROS) directly, but Cd-induced oxidative stress is a common phenomenon observed in multiple studies. The current review gives an overview on Cd-induced ROS production and anti-oxidative defense in organisms under different Cd regimes. Moreover, the Cd-induced oxidative challenge is discussed with a focus on damage and signaling as downstream responses. Gathering these data, it was clear that oxidative stress related responses are affected during Cd stress, but the apparent discrepancies observed in between the different studies points towards the necessity to increase our knowledge on the spatial and temporal ROS signature under Cd stress. This information is essential in order to reveal the exact role of Cd-induced oxidative stress in the modulation of downstream responses under a diverse array of conditions. 相似文献
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The present study has attempted to elucidate the alteration of serotonin turnover after 24 h REM sleep deprivation in different
regions in brain of young rat. Sleep deprivation was induced by the inverted flowerpot technique. Results of this study show
increased serotonin turnover after 24 h REM sleep deprivation in all the brain regions except in the hypothalamus. The decreased
5-HT ratio shows increased serotonin in the hypothalamus after 24 h sleep deprivation. This study indicates increased activity
of serotonergic neurons in the hypothalamus after 24 h sleep deprivation. This also indicates that the hypothalamus plays
a role in the immediate compensatory mechanism during 24 h REM sleep deprivation in young rats. 相似文献
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Seed oil of Celastrus paniculatus Willd. (CP) has been reported to improve memory and the methanolic extract (ME) of CP was shown to exhibit free-radical-scavenging properties and anti-oxidant effects in human non-immortalized fibroblasts. In the present study, we have investigated the free-radical-scavenging capacity of CP seed oil (CPO) and two extracts, an ethanolic extract (EE) and a ME. CPO and EE showed dose-dependent, free-radical-scavenging capacity, but to a lesser degree than observed for ME. Oxidative stress involves the generation of free radicals and free radical scavenging is one of the mechanisms of neuroprotection. We therefore investigated the effects of CPO, ME, and EE for protection against hydrogen peroxide (H(2)O(2))- and glutamate-induced neurotoxicity in embryonic rat forebrain neuronal cells (FBNC). Pre-treatment of neuronal cells with CPO dose-dependently attenuated H(2)O(2)-induced neuronal death. Pre-treatment with ME and EE partially attenuated H(2)O(2)-induced toxicity, but these extracts were less effective than CPO for neuronal survival. In H(2)O(2)-treated cells, cellular superoxide dismutase (SOD) activity was unaffected, but catalase activity was decreased and levels of malondialdehyde (MDA) were increased. Pre-treatment with CPO, ME, or EE increased catalase activity and decreased MDA levels significantly. Also, CPO pre-treatment attenuated glutamate-induced neuronal death dose-dependently. The activity of cellular acetylcholinesterase (AChE) was not affected by CPO, ME, or EE, suggesting that the neuroprotection offered by CPO was independent of changes in AChE activity. Taken together, the data suggest that CPO, ME, and EE protected neuronal cells against H(2)O(2)-induced toxicity in part by virtue of their antioxidant properties, and their ability to induce antioxidant enzymes. However, CPO, which exhibited the least antioxidant properties, was the most effective in preventing neuronal cells against H(2)O(2)- and glutamate-induced toxicities. Thus, in addition to free-radical scavenging attributes, the mechanism of CP seed component (CP-C) neuroprotection must be elucidated. 相似文献
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Wui Ann Woon Paul B. Ravindran Piyasiri Ekanayake Siti Amirah Yivonne Y.F. Lim Christopher H.S. Vun Jamsari Khalid 《Reports of Practical Oncology and Radiotherapy》2018,23(5):346-359
Aim
The aim of this study was to investigate the sensitivity of the trajectory log file based quality assurance to detect potential errors such as MLC positioning and gantry positioning by comparing it with EPID measurement using the most commonly used criteria of 3%/3?mm.Materials and methods
An in-house program was used to modified plans using information from log files, which can then be used to recalculate a new dose distribution. The recalculated dose volume histograms (DVH) were compared with the originals to assess differences in target and critical organ dose. The dose according to the differences in DVH was also compared with dosimetry from an electronic portal imaging device.Results
In all organs at risk (OARs) and planning target volumes (PTVs), there was a strong positive linear relationship between MLC positioning and dose error, in both IMRT and VMAT plans. However, gantry positioning errors exhibited little impact in VMAT delivery. For the ten clinical cases, no significant correlations were found between gamma passing rates under the criteria of 3%/3?mm for the composite dose and the mean dose error in DVH (r?<?0.3, P?>?0.05); however, a significant positive correlation was found between the gamma passing rate of 3%/3?mm (%) averaged over all fields and the mean dose error in the DVH of the VMAT plans (r?=?0.59, P?<?0.001).Conclusions
This study has successfully shown the sensitivity of the trajectory log file to detect the impact of systematic MLC errors and random errors in dose delivery and analyzed the correlation of gamma passing rates with DVH. 相似文献28.
Siti Maziras Makhtar Azlan Husin Abdul Aziz Baba Ravindran Ankathil 《Journal of genetics》2018,97(4):835-842
Imatinib mesylate (IM), a well-established gold standard drug in the treatment of chronic myeloid leukaemia (CML), is a synthetic tyrosine kinase inhibitor. Despite excellent efficacy, a significant number of patients on IM therapy develop resistance to IM. Currently, great focus has been laid on the effect of interindividual pharmacogenetic variability on IM treatment responses. IM uptake is mediated by the hOCT1 protein encoded by the solute carrier 22 gene (SLC22A1). The current study investigated the impact of few single-nucleotide polymorphisms (SNPs) of SLC22A1 on mediating resistance and/or good response to IM among 278 Malaysian CML patients (146 IM-resistant group and 132 IM good response group) undergoing IM therapy on 400 mg daily. Our results showed that the allelic frequencies of heterozygous (CG) and homozygous variant (GG) genotypes of SLC22A1 C480G were significantly higher in the IM-resistant group compared with the IM good response group (41.8% versus 30.3% and 10.9% versus 4.5% with P values of 0.047 and 0.048, respectively). On evaluating the association of genotypes with risk of IM resistance development, heterozygous (CG) and homozygous (GG) variant genotypes showed significantly higher risk for developing resistance to IM treatment with odds ratio (OR): 1.901 (95% confidence interval (CI): 1.142–3.163, \(P=0.013\)) and 3.324 (95% CI: 1.235–8.947, \(P=0.017\)), respectively. Two SNPs and two insertions/deletions were detected in exon 7 of SLC22A1. For exon 7, 1222AA carriers together with the presence of both the 8-bp insertion and 3-bp deletion, and M420del alleles showed higher possibility of developing resistance towards IM treatment. Our results warrant the need of genotyping this SNP in terms of modulating IM treatment in CML patients. 相似文献
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