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In contrast, anti-Fas stimulation altered this sequence: IETDase was the first measurable caspase activity and DEVDase preceded VEIDase. In an attempt to determine the intracellular target of the potent antiapoptotic agent carbobenzoxy-valyl-alanyl-aspartyl(β-methyl ester)-fluoromethyl ketone (Z-VAD[OMe]-FMK), we examined its ability to inhibit previously activated intracellular caspases. However, no significant reductions of these activities were observed. These fluorogenic caspase substrates allow direct observation of the caspase cascade in intact apoptotic cells, showing that the order of downstream caspase activation is dependent on the apoptotic stimulus.</jats:p>","journal":"The Journal of Experimental Medicine","year":2000,"id":606768,"datarank":0.7658918210850871,"base_score":5.10594547390058,"endowment":5.10594547390058,"self_citation_contribution":0.7658918210850871,"citation_network_contribution":0.0,"self_endowment_contribution":0.7658918210850871,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":164,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1557799,"name":"Beverly Z. 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Caspase activities were then assessed at various times after in vitro treatment of mouse thymocytes with dexamethasone or anti-Fas antibody. Dexamethasone induced the following order of appearance of caspase activities as judged by flow cytometry: LEHDase, WEHDase, VEIDase, IETDase, and DEVDase. Since the relative order of caspases 3 (DEVDase) and 6 (VEIDase) in the cascade has been controversial, this caspase activation order was reexamined using confocal microscopy. The VEIDase activity appeared before DEVDase in every apoptotic cell treated with dexamethasone. In contrast, anti-Fas stimulation altered this sequence: IETDase was the first measurable caspase activity and DEVDase preceded VEIDase. In an attempt to determine the intracellular target of the potent antiapoptotic agent carbobenzoxy-valyl-alanyl-aspartyl(β-methyl ester)-fluoromethyl ketone (Z-VAD[OMe]-FMK), we examined its ability to inhibit previously activated intracellular caspases. However, no significant reductions of these activities were observed. These fluorogenic caspase substrates allow direct observation of the caspase cascade in intact apoptotic cells, showing that the order of downstream caspase activation is dependent on the apoptotic stimulus.</jats:p>","is_dataset_classified":null,"base_score":5.10594547390058,"endowment":5.10594547390058,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10839799","pmcid":"PMC2213522","openalex_id":"https://openalex.org/W2067461742","authors":[],"funders":[],"total_grants":0,"fwci":7.4544,"citation_percentile":0.97969061,"influential_citations":0,"citation_trend":[{"year":2012,"count":4},{"year":2013,"count":1},{"year":2014,"count":4},{"year":2015,"count":3},{"year":2016,"count":6},{"year":2017,"count":2},{"year":2020,"count":1},{"year":2022,"count":3},{"year":2023,"count":1},{"year":2024,"count":3},{"year":2025,"count":3}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://rupress.org/jem/article-pdf/191/11/1819/1124080/991676.pdf","host_type":"journal"},{"url":"https://rupress.org/jem/article-pdf/191/11/1819/1124080/991676.pdf","host_type":"publisher"},{"url":"https://rupress.org/jem/article-pdf/191/11/1819/1695680/991676.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1084/jem.191.11.1819","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10839799","host_type":"repository"},{"url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.282.5623","host_type":""},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2213522","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC2213522","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC2213522?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Cell death mechanisms and regulation","Phagocytosis and Immune Regulation"],"mesh_terms":["Amino Acid Chloromethyl Ketones","Animals","Cell Extracts","Cell Membrane Permeability","Dexamethasone","Fluorescent Dyes","Intracellular Fluid","Mice, Inbred C57BL","Peptide Hydrolases","Peptides","Rhodamines","Substrate Specificity","Thymus Gland","Cysteine Proteinase Inhibitors","Apoptosis","Microscopy, Confocal","fas Receptor","Caspases","Mice"],"keywords":["Caspase","Apoptosis","Caspase 3","Intracellular","Cell biology","Biology","Caspase 8","Programmed cell death","Caspase 2","Flow cytometry","Molecular biology","Chemistry","Biochemistry"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T05:08:51.704275Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}