Caspase 3 Expressions in Children with Acute Lymphoblastic Leukemia During Induction Phase Chemotherapy
Lukman OktadiantoMia Ratwita AndarsiniI Dewa Gede UgrasenaYetti HernaningsihAndi CahyadiMaria Christina Shanty Larasati
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Introduction: Caspase-3 is a crucial mediator of the extrinsic apoptosis pathway. The role of caspase-3 for extrinsic apoptosis signalling is still a challenge and should be exploited in childhood ALL. This study aimed to compare the caspase-3 expression in the patient’s bone marrow before and after the induction phase of chemotherapy in childhood ALL. It will also to correlate the mean difference in caspase-3 expression between ALL standard-risk and ALL high-risk patients. Methods: Seventeen newly diagnosed ALL subjects were enrolled in this study. Caspase-3 expression in bone marrow was assessed using flow cytometry and monoclonal antibodies. A T-test and a paired T-test were used to compare between groups. The correlation coefficient between ALL groups was evaluated using Spearman’s test and linear regression with a significant p-value of 0.05. Results: The caspase-3 expression is higher after induction therapy. However, it showed an insignificant difference (16.56+12.91% vs 27.71+12.33%; p = 0.08, p > 0.05). The mean difference of caspase-3 in ALL high-risk groups was significantly higher than in ALL standard-risk groups with a positive correlation (p = 0.007, r = 0.756). Conclusion: The caspase-3 expression after induction phase chemotherapy was increased in all standard-risk and high-risk patients; other lymphoblast apoptosis markers need to be confirmed alongside caspase-3.Keywords:
Induction chemotherapy
Caspase-9
Acute lymphocytic leukemia
Objective To explore the effects of caspase-3 and caspase-8 on sodium fluoride(NaF)-induced apoptosis in human neuroblastoma SH-SY5Y cells. Methods The cell survival rate, percentage of apoptosis, caspase-3 activity and mRNA expression levels of caspase-3 and caspase-8 were determined respectively after the SH-SY5Y cells were exposed to 20, 40 and 80 μg/ml NaF for 24 hours in vitro. Furthermore, the changes of the percentage of apoptosis,caspase-3 activity and mRNA expression levels of caspase-3 and caspase-8 in 40 μg/ml NaF-treated groups incubated with activating or neutralizing anti-Fas antibody (CH11 or ZB4) also were observed respectively. Results Compared with the control group, the cell survival rates in 40 and 80 μg/ml NaF-treated groups were significantly lower (P＜0.0l). The percentage of apoptosis in 40 and 80 μg/ml NaF-treated groups were markedly higher than that in the control group (P＜0.05) and a dose-response trend was seen. The activity of caspase-3 and mRNA expression levels of caspase-3 and caspase-8 in 40 and 80 μg/ml NaF-treated groups were significantly higher than that in the control group (P＜0.05). CH11 showed a synergistic effect on fluoride-induced apoptosis when used in combination with NaF. ZB4 could partly block NaF-induced apoptosis of SH-SY5Y cells. Conclusion NaF can up-regulate the caspase-3 and caspase-8 expressions, which are the key enzymes of Fas pathway and subsequently promote apoptosis of SH-SY5Y cells.
SH-SY5Y
Sodium fluoride
Caspase-9
Caspase 8
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Oxidative stress is known to be involved in a variety of pathological processes including atherosclerosis, diabetes, and neurodegenerative diseases. Understanding how intracellular signaling pathways respond to oxidative stress will have a significant implication in the therapy of these diseases. In this study, we applied hydrogen peroxide (H2O2) to trigger apoptosis and investigated the dynamic activation of various caspases using a FRET technique. We measured the activation dynamics of caspase 3 and caspase 9 based on two reporter systems, SCAT 3 and SCAT 9. We found that caspase 3 activation was earlier than that of caspase 9 following H2O2 treatment. Caspase 3 was activated rapidly, reaching a maximum in 12±3 min, while the average duration of caspase 9 activation was 21±3 min. When cells were pretreated with Z-LEHD-fmk, a caspase 9 specific inhibitor, caspase 3 activation and apoptosis by H2O2 treatment were little affected, although the caspase 9 activation was completely inhibited. When cells were pretreated with Z-DEVD-fmk, a caspase 3 specific inhibitor, the activation of both caspase 3 and caspase 9, as well as apoptosis, were inhibited. When cells were pretreated with Z-IETD-fmk, a caspase 8 specific inhibitor, the activation of caspase 3 and caspase 9 were significantly delayed. Finally, we found that Bax did not translocate from the cytosol to the mitochondrial membrane during H2O2-induced apoptosis. Our results suggest that, during H H2O2-induced apoptosis, caspase 3 is activated directly through caspase 8 and is not through the mitochondria-dependent caspase 9 activation.
Caspase-9
Caspase 8
Caspase 2
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Caspase 2
Cleavage (geology)
NLRP1
Caspase-9
Nuclear export signal
Caspase 8
Caspase 10
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Objective Caspase and cytochrome C (Cyto.C) plays an important role in apoptosis in excitotoxic model. But caspase and Cyto C protein expression in excitotoxic model have not been report. Purpus of this research was exploring the protein expression and the mechanism of Caspase and Cyto C in KA indued neurotoxicity. Methods To made OHC model and test the Caspase and Cyto C protein expression by western blot. Results There are low level of Caspase 3 and Caspase 9 expression in control group. Caspase 3,Caspase 9 and Cyto C protein expression were significantly increased after KA treatment. Although active form of Caspase 3 (17KD) were not detected. Conclusions (1)There are low level of Caspase 3,Caspase 9 and cytochrome C expression in normal hippocampal neuron.(2)KA could increase Caspase 3,Caspase 9 and cytochrome C expression,indicating that KA could increase Cyto C releasing into cytosol,then Cyto. C further activate Caspase 9,actived Caspase 9 could activate Caspase 3,finally causing apoptosis.
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Neurotoxicity
Caspase 8
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Caspase 8
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Nerve growth factor- (NGF) induced potent activation of caspase-8, and caspase-9 in PC12 cells in a time-dependent manner. Peptide inhibition of caspase activity led to a potent reduction in neurite outgrowth in NGF-treated cells. Although NGF treatment resulted in cell-cycle G0/G1 arrest as detected by FACS cell-cycle analysis, caspase inhibitors (caspase-8 and caspase-9 inhibitors) could block the G0/G1 arrest in PC12 cells. We demonstrated the unique caspase cascade, caspase-8, caspase-3, and caspase-9 to occur, in this order. In conclusion, present results confirm a unique role for the caspase-8 and caspase-9 mediated signal cascade in the differentiation of PC12 cells.
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Neurite
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Caspase 2
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Human periodontal ligament (PDL) cells underwent apoptosis after mechanical stretch loading. However, the exact signalling pathway remains unknown. This study aimed to elucidate how the apoptotic caspases functioned in the cyclic stretch-induced apoptosis in human PDL cells.In the present study, 20% cyclic stretch was selected to load the cells for 6 or 24 h. The following parameters were analyzed: apoptotic rates, the protein levels of caspase-3, -7, -8 and -9 and the activities of caspase-8 and -9. Subsequently, the influences of caspase-8 and caspase-9 inhibitors on the apoptotic rate and the protein level of the activated caspase-3 were assessed as well.The apoptotic rates increased in response to cyclic stretch, but the cells entered different apoptotic stages after 6 and 24 h stretches. Caspase-3, -7, -8 and -9 were all activated after stretch loading. The stretch-induced apoptosis and the protein level of the activated caspase-3 were inhibited after inhibiting both caspase-8 and caspase-9 in both 6 and 24 h stretched cells and after inhibiting caspase-9 in 24 h stretched cells.Caspase-8 and -9 functioned differently at different apoptotic stages in human PDL cells after cyclic stretch.
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Satratoxins, which are produced Stachybotrys species, have been recognized as potential agents associated with sick building syndromes. In spite of the potential importance of satratoxins, the molecular mechanism induced by them remains unknown. Recently, we have found that satratoxin G induced potent apoptosis in HL-60 human promyelotic leukemia cells and both caspase-8 and caspase-9 are activator of caspase-3. However, the detail activation profile of caspases and role of the other caspases including caspase-6, caspase-7 and a novel initiator caspase, caspase-2 remain to be clear. Here we report detail caspase cascade in satratoxin G-induced apoptosis in HL-60 cells. Caspase assay with DEVD-AMC, a fluorogenic substrate, and western blot analysis of caspase-7 suggested that caspase-3 was involved, but casapase-7 was not directly involved in satratoxin-induced apoptosis. We investigated in-depth time courses of caspase activation. Caspase-3 was activated after 1 hour from satratoxin treatment. Activation of caspase-2 was observed apparently as early as 1 h. Caspase-9 was also activated significantly at the 1 hour time point. Caspase-6 and caspase-8 were activated at the 3-hour time point. Western blot analysis showed that cleavage of bid and activation of caspase-12 were not involved in satratoxin-mediated apoptosis. These findings suggest that the initial activators of caspase-3 are caspase-2 and casapse-9 in satatoxin-induced apoptosis. Because caspase-8 and casapse-9 were activated independently, caspase-8 is also involved in activation of caspase-3 in the late stage of the apoptosis. Moreover, caspase-6 appears to be associate with activation of caspase-8. Both caspase-7 and caspase-12 may be not potential caspases in the apoptosis.
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NLRP1
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Caspase 12
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细胞内部的反应的氧种类(ROS ) 被知道调整 apoptosis。caspase-9 的激活，在 mitochondrial apoptotic 串联的起始的 caspase，仔细与被联系 ROS，而是它是不清楚的是否 ROS 经由直接氧化的修正调整 caspase-9。阐明的现在的学习目的由哪个 ROS 调停的分子的机制 caspase-9 激活。我们的结果证明细胞的氧化状态便于 caspase-9 激活。氢过氧化物治疗引起 caspase-9 和 apoptosis 的激活，并且支持在 caspase-9 和 apoptotic 之间的一个相互作用激活朊酶的因素 1 (Apaf-1 ) 经由二硫化物形成。另外，在里面一在里面 vitro 没有线粒体的系统， thiol 氧化剂 diamide 由便于连接二硫化物的建筑群的形成支持 caspase-9 和 caspase-9/Apaf-1 相互作用的汽车劈开。最后，在 caspase-9 的 C403 的一个点变化通过二硫化物形成的废除损害有 Apaf-1 的两支持 H2O2 的 caspase-9 激活和相互作用。在细胞色素 c 和 C403S 异种之间的协会在细胞色素 c 和野类型的 caspase-9 之间是比那显著地弱的，显示 caspase-9 的那氧化修正贡献在氧化应力下面的 apoptosome 形成。一起拿，由 ROS 的 caspase-9 的氧化修正能调停它和 Apaf-1 的相互作用，和罐头因此支持它的汽车劈开和激活。这机制可以在氧化应力下面便于 apoptosome 形成和 caspase-9 激活。
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Caspase-9
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Late relapse of childhood lymphoblastic leukemia 10 years after the end of treatment is rare. A young woman whose acute lymphoblastic leukemia recurred 11 years after the end of treatment for acute lymphoblastic leukemia is described, and the literature on late relapse of childhood acute lymphoblastic leukemia is reviewed.
Acute lymphocytic leukemia
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