Death-mediating proteases such as caspases and caspase-3 in particular, have been implicated in neurodegenerative processes, aging and Alzheimer＇s disease. However, emerging evidence suggests that in addition to thei...Death-mediating proteases such as caspases and caspase-3 in particular, have been implicated in neurodegenerative processes, aging and Alzheimer＇s disease. However, emerging evidence suggests that in addition to their classical role in cell death, caspases play a key role in modulating synaptic function. It is remarkable that active caspases-3, which can trigger widespread damage and degeneration, aggregates in structures as delicate as synapses and persists in neurons without causing acute cell death. Here, we evaluate this dichotomy, and discuss the hypothesis that caspase-3 may be a bifurcation point in cellular signaling, able to orient the neuronal response to stress down either pathological/apoptotic pathways or towards physiological cellular remodeling. We propose that temporal, spatial and other regulators of caspase activity are key determinants of the ultimate effect of caspase-3 activation in neurons. This concept has implications for differential roles of caspase-3 activation across the lifespan. Specifically, we propose that limited caspase-3 activation is critical for synaptic function in the healthy adult brain while chronic activation is involved in degenerative processes in the aging brain.展开更多
Background Hypertensive intracerebral hemorrhage （HICH） is a severe disease with high morbidity and mortality. Timely removal of the hematoma through surgical procedures may effectively reduce secondary injuries. Ho...Background Hypertensive intracerebral hemorrhage （HICH） is a severe disease with high morbidity and mortality. Timely removal of the hematoma through surgical procedures may effectively reduce secondary injuries. However, there has long been a debate over the proper timing of such surgery. In this study, we explored the optimal operation time for HICH patients by observing the pathological changes in perihematomal brain regions during different stages of onset. Methods Twenty-five specimens of brain tissue, obtained from perihematomal region of HICH patients in different phases, were subjected to haematoxylin-eosin （HE） staining, terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end labeling （TUNEL） staining and Caspase-3, matrix metalloproteinases-9 （MMP-9） immunohistochemical staining. The changing roles of necrosis and apoptosis and the expression of MMP-9 and Caspase-3 positive cells were all observed using image analysis. Results The obvious expression of TUNEL positive cells was recognized within 6 hours of ICH onset, reaching its peak between 6 hours and 24 hours in the early phase. Results were highly consistent with Caspase-3 and MMP-9 positive cell counts. Necrosis was found 6 hours after ICH onset and aggravated after 12 hours. Conclusions In the early phase, apoptosis was seen as a major modality of injury in the brain tissue of the perihematomal region and was strongly correlated with the expression of MMP-9 and Caspase-3. The results of the present study suggest that an operation performed as soon as possible after ICH onset may be optimal for preserving the nervous system function.展开更多
AIM: To evaluate the role of survivin and caspase-3 in apoptosis of gastric carcinoma, as well as in prognosis of patients with gastric carcinoma.METHODS: Expressions of survivin and caspase-3 were investigated immuno...AIM: To evaluate the role of survivin and caspase-3 in apoptosis of gastric carcinoma, as well as in prognosis of patients with gastric carcinoma.METHODS: Expressions of survivin and caspase-3 were investigated immunohistochemically in 80 gastric carcinoma patients without a history of chemo-radiation therapy. Tumor cell apoptosis was examined by TUNEL method.RESULTS: Immunohistochemical analysis showed that survivin expression was positive in 61 of 80 patients (76%) with gastric carcinoma. In contrast, no expression of survivin in adjacent normal tissues was detected. Expression level of caspase-3 was higher in normal tissues than in carcinoma.Patients with higher expression of survivin had worse histological grades and pathological stages. Expression of caspase-3 was significantly associated with histological stages, but not with the pathological stages. Although survivin expression in carcinoma was not inversely related to caspase-3, patients with survivin (-) and caspase-3(+) had the maximum apoptosis index.CONCLUSION: Expression level of survivin was associated with histological grades and pathological stages of the tumor,indicating that survivin may be a poor prognosis factor for gastric carcinoma. Unlike caspase-3, survivin (an apoptosis inhibitor) can markedly inhibit the apoptosis of tumor cells.展开更多
Background Neuroblastoma, one of the common tumors in children, possesses the feature of natural regression that might be related to apoptosis caspase 3 and survivin are believed to respectively induce and inhibit apo...Background Neuroblastoma, one of the common tumors in children, possesses the feature of natural regression that might be related to apoptosis caspase 3 and survivin are believed to respectively induce and inhibit apoptosis. We investigated the expression of caspase 3 and survivin in pediatric neuroblastoma and the role that these genes played in apoptosis Methods The expression of caspase 3 and survivin in pediatric neuroblastoma tissue samples was detected using in situ hybridization, ter mintuesal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL), and immunohistochemical staining The role that these genes played in apoptosis was then evaluated Results A converse correlation was observed between the expression of survivin and caspase 3 When survivin was expressed at high levels in neuroblastoma samples, caspase 3 expression was downregulated, and the apoptotic index decreased simultaneously Conclusion There is a converse correlation between the expression of caspase 3 and the expression of survivin in neuroblastoma cells, indicating that caspase-3 might induce apoptosis, and survivin may inhibit this process展开更多
基金supported by a grant (AG012694-16) from the National Institue of Aging,USA
文摘Death-mediating proteases such as caspases and caspase-3 in particular, have been implicated in neurodegenerative processes, aging and Alzheimer＇s disease. However, emerging evidence suggests that in addition to their classical role in cell death, caspases play a key role in modulating synaptic function. It is remarkable that active caspases-3, which can trigger widespread damage and degeneration, aggregates in structures as delicate as synapses and persists in neurons without causing acute cell death. Here, we evaluate this dichotomy, and discuss the hypothesis that caspase-3 may be a bifurcation point in cellular signaling, able to orient the neuronal response to stress down either pathological/apoptotic pathways or towards physiological cellular remodeling. We propose that temporal, spatial and other regulators of caspase activity are key determinants of the ultimate effect of caspase-3 activation in neurons. This concept has implications for differential roles of caspase-3 activation across the lifespan. Specifically, we propose that limited caspase-3 activation is critical for synaptic function in the healthy adult brain while chronic activation is involved in degenerative processes in the aging brain.
文摘Background Hypertensive intracerebral hemorrhage （HICH） is a severe disease with high morbidity and mortality. Timely removal of the hematoma through surgical procedures may effectively reduce secondary injuries. However, there has long been a debate over the proper timing of such surgery. In this study, we explored the optimal operation time for HICH patients by observing the pathological changes in perihematomal brain regions during different stages of onset. Methods Twenty-five specimens of brain tissue, obtained from perihematomal region of HICH patients in different phases, were subjected to haematoxylin-eosin （HE） staining, terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end labeling （TUNEL） staining and Caspase-3, matrix metalloproteinases-9 （MMP-9） immunohistochemical staining. The changing roles of necrosis and apoptosis and the expression of MMP-9 and Caspase-3 positive cells were all observed using image analysis. Results The obvious expression of TUNEL positive cells was recognized within 6 hours of ICH onset, reaching its peak between 6 hours and 24 hours in the early phase. Results were highly consistent with Caspase-3 and MMP-9 positive cell counts. Necrosis was found 6 hours after ICH onset and aggravated after 12 hours. Conclusions In the early phase, apoptosis was seen as a major modality of injury in the brain tissue of the perihematomal region and was strongly correlated with the expression of MMP-9 and Caspase-3. The results of the present study suggest that an operation performed as soon as possible after ICH onset may be optimal for preserving the nervous system function.
文摘AIM: To evaluate the role of survivin and caspase-3 in apoptosis of gastric carcinoma, as well as in prognosis of patients with gastric carcinoma.METHODS: Expressions of survivin and caspase-3 were investigated immunohistochemically in 80 gastric carcinoma patients without a history of chemo-radiation therapy. Tumor cell apoptosis was examined by TUNEL method.RESULTS: Immunohistochemical analysis showed that survivin expression was positive in 61 of 80 patients (76%) with gastric carcinoma. In contrast, no expression of survivin in adjacent normal tissues was detected. Expression level of caspase-3 was higher in normal tissues than in carcinoma.Patients with higher expression of survivin had worse histological grades and pathological stages. Expression of caspase-3 was significantly associated with histological stages, but not with the pathological stages. Although survivin expression in carcinoma was not inversely related to caspase-3, patients with survivin (-) and caspase-3(+) had the maximum apoptosis index.CONCLUSION: Expression level of survivin was associated with histological grades and pathological stages of the tumor,indicating that survivin may be a poor prognosis factor for gastric carcinoma. Unlike caspase-3, survivin (an apoptosis inhibitor) can markedly inhibit the apoptosis of tumor cells.
文摘Background Neuroblastoma, one of the common tumors in children, possesses the feature of natural regression that might be related to apoptosis caspase 3 and survivin are believed to respectively induce and inhibit apoptosis. We investigated the expression of caspase 3 and survivin in pediatric neuroblastoma and the role that these genes played in apoptosis Methods The expression of caspase 3 and survivin in pediatric neuroblastoma tissue samples was detected using in situ hybridization, ter mintuesal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL), and immunohistochemical staining The role that these genes played in apoptosis was then evaluated Results A converse correlation was observed between the expression of survivin and caspase 3 When survivin was expressed at high levels in neuroblastoma samples, caspase 3 expression was downregulated, and the apoptotic index decreased simultaneously Conclusion There is a converse correlation between the expression of caspase 3 and the expression of survivin in neuroblastoma cells, indicating that caspase-3 might induce apoptosis, and survivin may inhibit this process
