Swati Dawar, Mariana Corrales Benitez, Yoon Lim, Toby A. Dite, Jumana M. Yousef, Niko Thio, Sylvain Garciaz, Thomas D. Jackson, Julia V. Milne, Laura F. Dagley, Wayne A. Phillips, Sharad Kumar, Nicholas J. Clemons,
Abstract Caspase-2, one of the most evolutionarily conserved members of the caspase family, is an important regulator of the cellular ... selenoenzyme glutathione peroxidase 4 (GPX4), we hypothesized that caspase-2 may play a role in regulating ferroptosis. ... demonstration of an important and unprecedented function of caspase-2 in protecting cancer cells from undergoing ferroptotic cell death. Specifically, we show that depletion of caspase-2 leads to the downregulation of stress response ... inducing compounds. Importantly, the canonical catalytic activity of caspase-2 is not required for its role and ...
Tópico(s): Cancer, Lipids, and Metabolism
2024 - Springer Nature | Cell Death and Disease
Hongmin Zhen, Yumeng Hu, Xiaoyan Liu, Guangsen Fan, Shuna Zhao,
Caspase-1 is one of the main mediators of inflammatory caspases and has become a correspondent with inflammation, cell ... systematically summarize both original and recent advances in caspase-1 to provide references for a better understanding ... study investigates and summarizes the published articles concerning caspase-1, inflammation, pyroptosis, apoptosis, and cell death by ... the PubMed, Web of Science, and Google Scholar. Caspase-1 is one of the main mediators of inflammatory caspases and has become a correspondent with inflammation and ...
Tópico(s): interferon and immune responses
2024 - Elsevier BV | Biochemical and Biophysical Research Communications
Nuray Üremiş, Meral Aslan, Elif Taşlıdere, Elif Gürel,
... molecular mechanisms of nicotine‐induced liver injury, the caspase cascade, and the Akt/NF‐κB signaling pathway, ... levels of Akt, NF‐κB, Bax, Bcl‐xL, Caspase‐3, and Caspase‐9, along with histopathological changes. Additionally, assessments of ... p‐Akt/Akt ratio, increased NF‐κB, Bax, Caspase‐3, and Caspase‐9 protein levels, and decreased the antiapoptotic protein ... inflammation, and apoptosis, mediated by Bax/Bcl‐xL, Caspase‐3, Caspase‐9, and Akt/NF‐κB pathways. Conversely, DEX ... liver injury by modulating apoptosis through NF‐κB, Caspase‐3, Caspase‐9, Bax inhibition, and Bcl‐xL ...
Tópico(s): Drug-Induced Hepatotoxicity and Protection
2024 - Wiley | Journal of Biochemical and Molecular Toxicology
José O. Castellón, Samuel Ofori, Nikolas R. Burton, Ashley R. Julio, Alexandra C. Turmon, Ernest Armenta, Carina Sandoval, Lisa M. Boatner, Evan E. Takayoshi, Marina Faragalla, C. Richard Taylor, Ann L. Zhou, Ky Tran, Jeremy Shek, Tianyang Yan, Heta S. Desai, Oliver I. Fregoso, Robert Damoiseaux, Keriann M. Backus,
Caspases are a highly conserved family of cysteine-aspartyl proteases known for their essential roles in regulating ... probes have emerged as useful tools for modulating caspase activity. However, due to the high sequence and structure homology of all 12 human caspases, achieving selectivity remains a central challenge for caspase-directed small-molecule inhibitor development efforts. Here, using ... highly reactive noncatalytic cysteine that is unique to caspase-2. By combining both gel-based activity-based ...
Tópico(s): RNA Interference and Gene Delivery
2024 - American Chemical Society | Journal of the American Chemical Society
Lingling Meng, Bufan Wu, Ling OuYang, Rou Peng, Yonglin Chen, Tang Zhi-juan, Min Zhang, Tanqing Xu, Yaling Wang, Sheng-Feng Lu, Xinyue Jing, Shuping Fu,
BackgroundImbalances between Bcl-2 and caspase-3 are significant evidence of apoptosis, which is considered an influential factor in rapidly occurring neuronal cell death and the decline ... increase in Bcl-2 or a reduction in caspase-3 exposure. The current study aimed to investigate whether acupuncture could modulate Bcl-2 and caspase-3 expression through histone acetylation modifications, which could ... damage following stroke. The expression of Bcl-2/caspase-3 mRNA was detected by real-time fluorescence ...
Tópico(s): Barrier Structure and Function Studies
2024 - Elsevier BV | Heliyon
Zachary P. Billman, Stephen B. Kovacs, Bo Wei, Kidong Kang, Ousmane H. Cissé, Edward A. Miao,
... trigger pyroptosis: GSDMA, B, C, D, and E. Caspase and granzyme proteases cleave the linker regions of ... GSDMA. Remarkably, GSDMA in numerous bird species contain caspase-1 cleavage sites like YVAD or FASD in ... birds, amphibians, and reptiles are all cleaved by caspase-1. Thus, GSDMA was originally cleaved by the host-encoded protease caspase-1. In mammals the caspase-1 cleavage site in GSDMA is disrupted; instead, a new protein, GSDMD, is the target of caspase-1. Mammal caspase-1 uses exosite interactions with ...
Tópico(s): Autoimmune and Inflammatory Disorders Research
2024 - eLife Sciences Publications Ltd | eLife
Alexander I. M. Sever, T. Reid Alderson, Enrico Rennella, James M. Aramini, Zi Hao Liu, Robert W. Harkness, Lewis E. Kay,
... heptameric protein scaffold that recruits and activates the caspase-9 protease. Once activated, caspase-9 cleaves and activates downstream effector caspases, triggering the onset of cell death through caspase-mediated proteolysis of cellular proteins. Failure to activate caspase-9 enables the evasion of programmed cell death, ... of cancer. Despite the critical apoptotic function of caspase-9, the structural mechanism by which it is ... and biochemical assays to study the activation of caspase-9 bound to the apoptosome. In the absence ...
Tópico(s): Endoplasmic Reticulum Stress and Disease
2023 - National Academy of Sciences | Proceedings of the National Academy of Sciences
Maricarmen Rojas-López, María Luisa Gil-Marqués, Vritti Kharbanda, Amanda S. Zajac, Kelly A. Miller, Thomas E. Wood, Austin C. Hachey, Keith T. Egger, Marcia B. Goldberg,
... induces the assembly of an inflammasome that contains caspases-4/5 in humans or caspase-11 in mice. Whereas activation of all other ... receptors for cLPS exist has remained unclear, because caspase-4, caspase-5, and caspase-11 bind and activate LPS directly in vitro. ... that is required for efficient activation of the caspase-4 inflammasome in human macrophages. In human macrophages, NLRP11 is required for efficient activation of caspase-4 during infection with intracellular Gram-negative bacteria ... of LPS. NLRP11 could bind LPS and separately caspase-4, forming a high-molecular weight complex with ...
Tópico(s): Immune Response and Inflammation
2023 - American Association for the Advancement of Science | Science Immunology
Cynthia T. Luk, Carmen K. Chan, Felix Chiu, Sally Yu Shi, Paraish S. Misra, Yu Zhe Li, Evan Pollock‐Tahiri, Stephanie A. Schroer, Harsh R. Desai, Tharini Sivasubramaniyam, Erica P. Cai, Mansa Krishnamurthy, Daniel J. Han, Apu Chowdhury, Rukhsana Aslam, Darren A. Yuen, Anne Hakem, Razqallah Hakem, Minna Woo,
Caspases are cysteine-aspartic proteases that were initially discovered to play a role in apoptosis. However, caspase 8, in particular, also has additional nonapoptotic roles, ... diabetes. Here, we examined the pleiotropic role of caspase 8 in adipocytes and obesity-associated insulin resistance. Caspase 8 expression was increased in adipocytes from mice ... insulin resistance. Treatment of 3T3-L1 adipocytes with caspase 8 inhibitor Z-IETD-FMK decreased both death ... We generated novel adipose tissue and adipocyte-specific caspase 8 knockout mice (aP2Casp8-/- and adipoqCasp8-/-). Both males ...
Tópico(s): Biomarkers in Disease Mechanisms
2023 - American Diabetes Association | Diabetes
Joo‐Hui Han, Rebecca E. Tweedell, Thirumala‐Devi Kanneganti,
... for characterizing innate immune PCD activation by monitoring caspases, a family of cysteine-dependent proteases that are ... apoptosis, pyroptosis, necroptosis, and PANoptosis. Initial reports characterized caspase-2, caspase-8, caspase-9, and caspase-10 as initiator caspases and caspase-3, caspase-6, and caspase-7 as effector caspases in apoptosis, while later ...
Tópico(s): Cell death mechanisms and regulation
2023 - MyJOVE | Journal of Visualized Experiments
Sebastian Hughes, Meng Lin, Ashley Weir, Bing Huang, Liya Xiong, Ngee Kiat Chua, Jiyi Pang, Jascinta P. Santavanond, Rochelle Tixeira, Marcel Doerflinger, Yexuan Deng, Chien‐Hsiung Yu, Natasha Silke, Stephanie A. Conos, Daniel Frank, Daniel S. Simpson, James M. Murphy, Kate E. Lawlor, Jaclyn S. Pearson, John Silke, Marc Pellegrini, Marco J. Herold, Ivan K. H. Poon, Seth L. Masters, Mingsong Li, Qin Tang, Yuxia Zhang, Maryam Rashidi, Lanlan Geng, James E. Vince,
... 1β maturation as well as cell death–associated caspase‐8 and Gasdermin D (GSDMD) processing in diseased ... upon patient treatment. Loss of XIAP leads to caspase‐8‐driven cell death and bioactive IL‐1β ... and pyroptotic cell death machinery. Namely, extrinsic apoptotic caspase‐8 promotes pyroptotic GSDMD processing that kills macrophages lacking both inflammasome and apoptosis signalling components (caspase‐1, ‐3, ‐7, ‐11 and BID), while caspase‐8 can still cause cell death in the absence of both GSDMD and GSDME when caspase‐3 and caspase‐7 are present. Neither caspase‐ ...
Tópico(s): Streptococcal Infections and Treatments
2023 - Springer Nature | The EMBO Journal
Nitin Srivastava, Anil K. Saxena,
... worldwide. Among different targets to design anticancer agents, caspase-3 is an important target as its cleavage ... molecules, many small molecules have been reported as caspase-3 activators.In view of the above, the ... the published work on small molecules reported as caspase-3 activators and their anticancer activity to get ... etc. for the publications of small molecules as caspase-3 activators inducing apoptosis in cancer cells.In this review, the small molecules showing caspase-3 cleavage and activation have been discussed under ...
Tópico(s): Cell death mechanisms and regulation
2023 - Bentham Science Publishers | Current Protein and Peptide Science
Amy H. Chan, Sabrina Sofia Burgener, Kassandra Vezyrgiannis, Xiaohui Wang, Jadie Acklam, Jessica B. von Pein, Malvina Pizzuto, Larisa I. Labzin, Dave Boucher, Kate Schroder,
... inflammasome pathway involves unleashing the proteolytic activity of caspase-4 within this complex. Caspase-4 induces inflammatory responses by cleaving gasdermin-D ( ... initiate pyroptosis; however, the molecular mechanisms that activate caspase-4 and govern its capacity to cleave substrates remain poorly defined. Caspase-11, the murine counterpart of caspase-4, acquires protease activity within the noncanonical inflammasome ... cleavage events trigger signalling via the NLRP3-ASC-caspase-1 axis, leading to downstream cleavage of the ...
Tópico(s): Immune Cell Function and Interaction
2023 - | Life Science Alliance
Pascal Devant, Ying Dong, Julian Mintseris, Weiyi Ma, Steven P. Gygi, Hao Wu, Jonathan C. Kagan,
Inflammatory caspases are key enzymes in mammalian innate immunity that control the processing and release of interleukin-1 (IL- ... the biological importance, the structural basis for inflammatory caspase-mediated cytokine processing has remained unclear. To date, ... pro-IL-18, has been attributed primarily to caspase-1 activities within canonical inflammasomes3. Here we demonstrate that the lipopolysaccharide receptor caspase-4 from humans and other mammalian species (except ... cleavage by the prototypical IL-1-converting enzyme caspase-1. This ability of caspase-4 to cleave ...
Tópico(s): Cell death mechanisms and regulation
2023 - Nature Portfolio | Nature
V. S. Belousova, О. А. Свитич, Е.В. Тимохина, И.В. Игнатко, И.М. Богомазова, Svetlana Pesegova, Tatiana Silaeva, T. I. Kuzmina, Oxana Skorobogatova,
... PTB. We evaluated gene expression involved in apoptosis: caspase-3, caspase-8, and XIAP (X-linked inhibitor of apoptosis) ... and PCR. During pregnancy the gene expression of caspase-3 and caspase-8 is low, but XIAP is higher than the caspases. At the onset of preterm labour, we observed a significantly increased expression of both caspase-8 (10.7-fold, p < 0.01) and caspase-3 (2.5-fold, p < 0.01) and ... study showed that during pregnancy, the expression of caspase genes in the placenta is low and probably ...
Tópico(s): Neonatal Respiratory Health Research
2023 - Multidisciplinary Digital Publishing Institute | International Journal of Molecular Sciences
Zachary P. Billman, Stephen B. Kovacs, Bo Wei, Kidong Kang, Ousmane H. Cissé, Edward A. Miao,
... trigger pyroptosis: GSDMA, B, C, D, and E. Caspase and granzyme proteases cleave the linker regions of ... GSDMA. Remarkably, GSDMA in numerous bird species contain caspase-1 cleavage sites like YVAD or FASD in ... birds, amphibians, and reptiles are all cleaved by caspase-1. Thus, GSDMA was originally cleaved by the host-encoded protease caspase-1. In mammals the caspase-1 cleavage site in GSDMA is disrupted; instead, a new protein, GSDMD, is the target of caspase-1. Mammal caspase-1 uses exosite interactions with ...
Tópico(s): Autoimmune and Inflammatory Disorders Research
2023 - eLife Sciences Publications Ltd | eLife
Isabel M. Alonso-Bellido, Mercedes Posada-Pérez, Francisco Hernández-Rasco, Sandra Vázquez‐Reyes, María Isabel Calle Cabanillas, Antonio J. Herrera, Sara Bachiller, Jesús Soldán-Hidalgo, Ana M. Espinosa‐Oliva, Bertrand Joseph, Rocío M. de Pablos, José L. Venero, Rocío Ruiz,
... of new neurons along the rostral migratory stream. Caspase-3 is a cysteine-aspartate-protease classically considered as one of the main effector caspases in the cell death program process. In addition ... present study is to identify the role of Caspase-3 in neurogenesis-related microglial functions. To address this study, Caspase-3 conditional knockout mice in the microglia cell ... adult neurogenesis takes place. After the reduction of Caspase-3 in microglia, mutant mice showed a reduction ... a reduction in doublecortin-positive neurons in conditional Caspase-3 knockout mice, which corresponds to a reduction ...
Tópico(s): Inflammation biomarkers and pathways
2023 - Elsevier BV | Brain Behavior and Immunity
Ozlem Calbay, Ravi N. Padia, Mahmuda Akter, Lei Sun, Bin Li, Nicole Qian, Jianhui Guo, Zheng Qing Fu, Lingtao Jin, Shuang Huang,
... type of programmed cell death depending on active caspase-1, and the inflammasome carries out caspase-1 activation. Here, we showed that docosahexaenoic acid (DHA) induced ovarian cancer cell deaths in caspase-1-dependent manner. DHA increased caspase-1 activity and led to interleukin-1β secretion ... DHA triggered pyroptosis. Intriguingly, ASC, the molecule recruiting caspase-1 to inflammasome for activation, was dispensable for ... induced pyroptosis. Instead, we observed remarkable elevation in caspase-1 abundance concurrent with the activation of caspase- ...
Tópico(s): Inflammasome and immune disorders
2023 - Cell Press | iScience
Julian Ramelow, Yacob Keleta, Guodong Niu, Xiaohong Wang, Jun Li,
... that Pfs16 reduced the activity of mosquito midgut caspase 3/7, a key enzyme in the mosquito ... that Pfs16 reduced the activity of mosquito midgut caspase 3/7, a key enzyme in the mosquito ... apoptosis, immunity, and cell proliferation by activating specific caspases (21Boutros M. Agaisse H. Perrimon N. Sequential activation ... immunity.PLoS Pathog. 2013; 9e1003622Google Scholar). Indeed, the caspase activities are used to monitor the activation of ... antibodies and rPfs16 protein on the activities of caspase 3/7, key enzymes in JNK pathway, in ...
Tópico(s): Insect Resistance and Genetics
2023 - Elsevier BV | Journal of Biological Chemistry
Bustanur Rosidi, Diana Priyatno, T.P. Putra, Irawan Yusuf,
... apoptosis and cell death of HCT116 and SW620. Caspase 3 activities were measured in caspase-3 activity tests using a caspase-3 activity kit. Furthermore, Western blots were performed with anti-PARP1, anti-caspase 3, and anti-cleaved caspase 3 to confirm whether caspase activation was present or not.Both MTS proliferation ... induced cell death in both cell lines. However, caspase 3 activity could not be detected. Cleavage of both PARP1 and pro-caspase 3 was not observed in the Western blot, confirming the absence of caspase 3 activations.This present study suggests a caspase ...
Tópico(s): Cancer-related Molecular Pathways
2023 - Dove Medical Press | Cancer Management and Research
Mingwei Sheng, Yiqi Weng, Yingli Cao, Chen Zhang, Yuanbang Lin, Wenli Yu,
... reperfusion (IR) injury has not been fully clarified. Caspase 6 is a critical regulator in innate immunity ... We aimed to characterize the specific role of Caspase 6 in IR-induced inflammatory responses in fatty ... from patients undergoing ischemia-related hepatectomy to evaluate Caspase 6 expression. in mice model, we generated Caspase 6-knockout (Caspase 6KO) mice to investigate cellular and molecular mechanisms of macrophage Caspase 6 in IR-stimulated fatty livers. In human liver biopsies, Caspase 6 expression was upregulated combined with enhanced serum ...
Tópico(s): Hepatitis Viruses Studies and Epidemiology
2023 - Springer Nature | Cell Death Discovery
Xijie Dong, Hao Tu, Xiangjun Bai, Shuang Qin, Zhanfei Li,
... group. The expression of Bcl-2, CD95, cleaved caspase-9/8, and activated caspase-3/1 in the B cell subsets were ... patients were recruited to test the remission of caspase-3 (Z-DEVD-FMK) and -1 (VX-765) ... B cells decreased and the levels of cleaved caspase-9 in IM B cells increased; The levels ... AM) B cells and the levels of cleaved caspase-8 in IM, RM, and AM B cells increased; The levels of activated caspase-3 and caspase-1 in IM, RM, and AM B cells increased. Activated caspase-1 levels in IM B cells were higher ...
Tópico(s): Inflammasome and immune disorders
2023 - Lippincott Williams & Wilkins | Shock
Stephanie M. Bozonet, Nicholas J. Magon, Abigail J. Schwartfeger, Andreas Königstorfer, Sarah G. Heath, Margreet C.M. Vissers, Vanessa K. Morris, Christoph Göbl, James M. Murphy, Guy S. Salvesen, Mark B. Hampton,
... like protein by receptor-interacting protein kinase 3. Caspase-8 cleaves receptor-interacting protein kinases to block necroptosis, so synthetic caspase inhibitors are required to study this process in experimental models. However, it is unclear how caspase-8 activity is regulated in a physiological setting. The active site cysteine of caspases is sensitive to oxidative inactivation, so we hypothesized ... oxidants generated at sites of inflammation can inhibit caspase-8 and promote necroptosis. Here, we discovered that ...
Tópico(s): Inflammasome and immune disorders
2023 - Elsevier BV | Journal of Biological Chemistry
Jingying Wu, Siming Lin, Weixiao Chen, Guili Lian, Weibin Wu, Ai Chen, Mohammad Ismail Hajary Sagor, Li Luo, Huajun Wang, Liangdi Xie,
... of GSDME-mediated pyroptosis and activation of apoptotic caspase-8/-3 were also found in skeletal muscle ... triggered GSDME-mediated pyroptosis in myotubes through activating caspase-8 and caspase-3 by using caspase-8 and caspase-3 inhibitors. Comparing the activation of caspase-8 and GSDME expression between TNF Complex IIa ... inclined to assemble TNF Complex IIb in activating caspase-8 and triggering pyroptosis. Moreover, pyroptotic myotubes were ...
Tópico(s): Autoimmune and Inflammatory Disorders Research
2023 - Springer Nature | Cell Death Discovery
... this complexity arises from the diverse functions of caspase-8, a cysteine-aspartic acid protease typically associated with activating caspase-3 and - 7 to induce apoptosis. However, recent research has revealed that caspase-8 also plays a role in regulating the ... and T-cell signalling. In mice, loss of caspase-8 results in embryonic lethality from unrestrained necroptotic killing, while in humans caspase-8 deficiency can lead to an autoimmune lymphoproliferative ... periodic fevers. This review focuses on non-canonical caspase-8 signalling that drives immune responses, including its ...
Tópico(s): Gout, Hyperuricemia, Uric Acid
2023 - Elsevier BV | Seminars in Immunology
Mingxing Li, Xuejiao Sun, Zongqin Wang, Yi Li,
... have been implicated in the pathophysiology of MDD. Caspase-1, a classic inflammatory caspase, regulates AMPARs-mediated glutamatergic neurotransmission. However, the role of caspase-1 in chronic stress-induced GABAergic dysfunction remains ... this study, we found that serum and hippocampal caspase-1-IL-1β levels increased significantly in chronic ... a significant negative correlation occurred between levels of caspase-1 and depression-like behaviors. Furthermore, CRS significantly ... γ2 subunit in the hippocampus. Genetic deficiency of caspase-1 not only blocked CRS-induced depression-like ...
Tópico(s): Vagus Nerve Stimulation Research
2023 - Springer Nature | Translational Psychiatry
Chenyang Han, Hongyan Pei, Yongjia Sheng, Jin Wang, Xiaohong Zhou, Wenyan Li, Guo Li, Yun Kong, Yi Yang,
... and network pharmacological analysis was performed to identify Caspase-3 as the target of TRI-induced liver ... was assessed after knocking out GSDMD, GSDME and Caspase-3 in cells, respectively. We also investigated the ... network pharmacology, indicating that TRI could bind to Caspase-3-VAL27 site to promote the cleavage of Caspase-3, and Cleaved-Caspase-3 induced pyroptosis of Kupffer cells through GSDME ... mutation of VAL27, TRI could not bind to Caspase-3. Animal-level results showed that TRI could induce liver injury in mice, while Caspase-3 knockout or Caspase-3 inhibitors could antagonize ...
Tópico(s): Autoimmune and Inflammatory Disorders Research
2023 - Elsevier BV | Ecotoxicology and Environmental Safety
Ebubekir Dirican, Halil Özcan, Sevgi Karabulut Uzunçakmak, Uğur Takım,
... programmed cell death that occurs by several pathways. Caspase-3 is induced by active caspase-9 via the intrinsic pathway. The aim of this research was to explore the expression of caspase-3 and caspase-9 in schizophrenia patients and healthy samples.RNA ... time PCR (RT-PCR) was used to analyse caspase-3 and caspase-9 gene expression. The severity of psychopathological symptoms ...
Tópico(s): Hippo pathway signaling and YAP/TAZ
2023 - | Clinical Psychopharmacology and Neuroscience
Carol MWALE, Takafumi SUNAGA, Yanlin Wang, Eugene C. Bwalya, Suranji Wijekoon, Sangho Kim, Masahiro Okumura,
... their in vitro effects on cell viability and caspase activity to elucidate whether they activate the extrinsic ... Counting Kit-8 (CCK-8) assays. Evaluation of caspase-3, caspase-8, and caspase-9 activity was performed using colorimetric assays. The ... assays were used to evaluate the effect of caspase inhibitors on local anesthetic chondrotoxicity. All three local ... both the extrinsic and intrinsic pathways. Bupivacaine increased caspase-3, caspase-8, and caspase-9 activity (P<0.001). Levobupivacaine increased caspase- ...
Tópico(s): Osteoarthritis Treatment and Mechanisms
2023 - Japanese Society of Veterinary Science | Journal of Veterinary Medical Science
Maddalena Nano, James A. Mondo, Jacob Harwood, Varuzhan Balasanyan, Denise J. Montell,
Executioner-caspase activation has been considered a point-of-no-return in apoptosis. However, numerous studies report survival from caspase activation after treatment with drugs or radiation. An ... question is whether cells can recover from direct caspase activation without pro-survival stress responses induced by ... we engineered a HeLa cell line to express caspase-3 inducibly and combined it with a quantitative caspase activity reporter. While high caspase activity levels killed all cells and very low ...
Tópico(s): CRISPR and Genetic Engineering
2023 - National Academy of Sciences | Proceedings of the National Academy of Sciences