Nuclear entry of active caspase-3 is facilitated by its p3-recognition-based specific cleavage activity

Luo, Min; Lu, Zhongxin; Sun, He; Yuan, Kehu; Zhang, Quancang; Meng, Sha; Wang, Fangxun; Guo, Hong-Chun; Ju, Xiaofang; Liu, Yuqing; Ye, Tao; Lu, Zhigang; Zhai, Zhonghe

doi:10.1038/cr.2010.9

Cited by 55 publications

(50 citation statements)

References 28 publications

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“…Nuclear translocation of cleaved caspase 3 as a harbinger of apoptosis has been noted in rat neuronal cells (50), human cervical epithelial cells (30), human epithelial hepatocytes (27,28), and human epithelial small cell lung cancer cells (29). Interestingly, the majority of cell types that demonstrate this phenomenon are parenchymal epithelial cells in origin.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies, however, suggest that nuclear translocation of caspase 3 is in fact an active process in apoptosis (27)(28)(29). Furthermore, nuclear translocation of caspase 3 seems to be necessary for the execution of apoptosis (26)(27)(28)(29)(30). Kamada and colleagues (28) demonstrated that a mutated caspase 3 that is unable to be activated does not translocate to the nucleus on stimulation with anti-fas treatment, implicating proteolytic activation as a necessary step for nuclear translocation.…”

Section: Discussionmentioning

confidence: 99%

“…Kamada and colleagues (28) demonstrated that a mutated caspase 3 that is unable to be activated does not translocate to the nucleus on stimulation with anti-fas treatment, implicating proteolytic activation as a necessary step for nuclear translocation. Although activation of caspase 3 is necessary for nuclear translocation, the necessity of cleaved caspase 3's functional activity for nuclear translocation is less certain (28,30). Despite increased interest in the mechanisms of nuclear translocation of caspase 3, the molecular machinery necessary for this process has not been elucidated.…”

Section: Discussionmentioning

confidence: 99%

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Mitogen-Activated Protein Kinase–Activated Protein Kinase 2 Mediates Apoptosis during Lung Vascular Permeability by Regulating Movement of Cleaved Caspase 3

Damarla

Parniani

Johnston

et al. 2014

Am J Respir Cell Mol Biol

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Apoptosis is a key pathologic feature in acute lung injury. Animal studies have demonstrated that pathways regulating apoptosis are necessary in the development of acute lung injury, and that activation of p38 mitogen-activated protein kinase (MAPK) is linked to the initiation of the apoptotic cascade. In this study, we assessed the role of the MAPK-activated protein kinase (MK) 2, one of p38 MAPK's immediate downstream effectors, in the development of apoptosis in an animal model of LPS-induced pulmonary vascular permeability. Our results indicate that wild-type (WT) mice exposed to LPS demonstrate increased apoptosis, as evidenced by cleavage of caspase 3 and poly (ADP-ribose) polymerase 1 and increased deoxynucleotidyl transferase-mediated dUDP nick-end labeling staining, which is accompanied by increases in markers of vascular permeability. In contrast, MK2 2/2 mice are protected from pulmonary vascular permeability and apoptosis in response to LPS. Although there was no difference in activation of caspase 3 in MK2 2/2 compared with WT mice, interestingly, cleaved caspase 3 translocated to the nucleus in WT mice while it remained in the cytosol of MK2 2/2 mice in response to LPS. In separate experiments, LPS-induced apoptosis in human lung microvascular endothelial cells was also associated with nuclear translocation of cleaved caspase 3 and apoptosis, which were both prevented by MK2 silencing. In conclusion, our data suggest that MK2 plays a critical role in the development of apoptosis and pulmonary vascular permeability, and its effects on apoptosis are in part related to its ability to regulate nuclear translocation of cleaved caspase 3.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Mitogen-Activated Protein Kinase–Activated Protein Kinase 2 Mediates Apoptosis during Lung Vascular Permeability by Regulating Movement of Cleaved Caspase 3

Damarla

Parniani

Johnston

et al. 2014

Am J Respir Cell Mol Biol

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“…In the present work we showed nuclear translocation of caspase 3 in some acinar cells. A previous study stated that Pro-caspase 3 may translocate from the cytoplasm to the nucleus and may be activated in both cellular compartments [23] .…”

Section: Discussionmentioning

confidence: 99%

Effect of Orlistat on the pancreas of the female albino rat: Histological and Histochemical study

Abdelwahab

Ali

Mahmoud

2017

Journal of Medical Histology

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Introduction: Orlistat is the only FDA approved drug for long term management of obesity. It reduces the absorption of dietary fat by inhibiting lipase enzyme. Many cases of pancreatitis were clinically reported in people who used orlistat. Aim of The work:The aim of the present study is to shed a light on the possible deleterious effect of orlistat on the normal pancreatic tissue, and the molecular mechanisms beyond these changes. Materials & Methods: Thirty six female albino rats were divided into 4 groups: Control Group I (a) without treatment &I (b) received only1 ml fish oil. Group II received 30 mg/kg/day of orlistat dissolved in 1ml of fish oil orally for 8 weeks. Group III, received 40 mg/kg/day of orlistat .Group IV (a) & (b) withdrawal groups. Pancreas was dissected out and processed for histological and immunohistochemical study for CASPASE, TNF, INOS and INSULIN. Results: Orlistat caused variable degrees of pancreatic tissue degeneration, dilatation of pancreatic ducts with retained secretion, fatty degeneration and congestion. Inflammatory cells infiltration observed in both pancreatic acini and islets of Langerhan,s only with high dose (40mg/kg). Positive immunoreactivity for activated caspase 3 and iNOS being more evident in high dose and decrease in immunoreactivity for anti-insulin antibody. immunoreactivity for TNF-α had been shown in high dose. These effects disappear after low dose withdrawal only. Conclusion: Orlistat may induce inflammation, fatty degeneration and impaired insulin production in the pancreas. These effects are dose dependent, and it should be taken in consideration while prescribing orlistat as a treatment for obesity.

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“…Caspase 3 functions in the cleavage of structural proteins, DNA repair enzymes, and activates endonucleases that cause DNA fragmentation in apoptotic mechanisms [27]. Caspase 3 as the executor or effector on the apoptotic process may play an important role in assessing the response or resistance of a cell to chemotherapy or cytotoxic substances [28].…”

Section: Siregar Et Almentioning

confidence: 99%

Evaluation of Caspase 3 as an Indicator for Breast Cancer Chemotherapy Response

Siregar

Manuaba

Lubis

et al. 2018

Asian J Pharm Clin Res

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Objectives: This study aimed to assess the difference of postchemotherapy caspase 3 level between triple negative breast cancer (TNBC) subjects with and without clinical response. Methods:A total of 48 subjects with intraductal and 12 subjects with intralobular TNBC who were undergoing surgery at Adam Malik General Hospital were analyzed the response of neoadjuvant chemotherapy. Postsurgical breast tumor tissue was treated in pathology laboratory for caspase 3 analysis. The data were processed in SPSS 22 with significance limitation of 0.05. Results:Median levels of caspase 3 postchemotherapy were higher both in intraductal and intralobular TNBC subtype (6 vs. 4.5 and 5 vs. 3, respectively) responsive group, while no changes detected in the group without clinical response. In statistical analysis, there was a significant difference of caspase 3 level postchemotherapy only in group with clinical response (p=0.005 in intraductal carcinoma and p=0.0031 in intralobular carcinoma). Conclusion:Postchemotherapy caspase 3 level increased significantly in TNBC, either intraductal or intralobular subtype, subjects with clinical response, but not in subjects without clinical response.

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Nuclear entry of active caspase-3 is facilitated by its p3-recognition-based specific cleavage activity

Cited by 55 publications

References 28 publications

Mitogen-Activated Protein Kinase–Activated Protein Kinase 2 Mediates Apoptosis during Lung Vascular Permeability by Regulating Movement of Cleaved Caspase 3

Mitogen-Activated Protein Kinase–Activated Protein Kinase 2 Mediates Apoptosis during Lung Vascular Permeability by Regulating Movement of Cleaved Caspase 3

Effect of Orlistat on the pancreas of the female albino rat: Histological and Histochemical study

Evaluation of Caspase 3 as an Indicator for Breast Cancer Chemotherapy Response

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