Print Email Facebook Twitter Stimulation of tissue-type plasminogen activator gene expression by sodium butyrate and trichostatin A in human endothelial cells involves histone acetylation Title Stimulation of tissue-type plasminogen activator gene expression by sodium butyrate and trichostatin A in human endothelial cells involves histone acetylation Author Arts, J. Lansink, T. Grimbergen, J. Toet, K.H. Kooistra, T. Instituut voor verouderings- en vaatziekten onderzoek TNO Publication year 1995 Abstract We have previously shown that the pleiotropic agent sodium butyrate strongly stimulates tissue-type plasminogen activator (t-PA) expression in human umbilical vein endothelial cells (HUVEC). Here we provide the following evidence that the butyrate-induced t-PA expression in HUVEC involves histone H4 acetylation. (1) t-PA induction by butyrate occurs at the transcriptional level and does not require new protein synthesis, indicating a direct effect. (2) t-PA induction by butyrate can be fully mimicked by a specific, structurally unrelated, histone deacetylase inhibitor, trichostatin A. (3) At optimally stimulatory conditions, a combination of butyrate and trichostatin A does not enhance t-PA production more than each of the compounds alone, indicating that:both compounds act through a common regulatory mechanism. (4) Induction of t-PA transcription by butyrate and trichostatin A was found to be preceded by histone H4 acetylation; at suboptimal inducing concentrations of butyrate and trichostatin A, the degree of acetylation of histone H4 caused by each agent was similarly reduced. These results are consistent with a role for histone H4 acetylation in t-PA induction by butyrate in HUVEC. Chemicals/CAS: butyric acid, 107-92-6, 156-54-7, 461-55-2; histone deacetylase, 9076-57-7; tissue plasminogen activator, 105913-11-9; trichostatin A, 58880-19-6; Butyric Acid, 107-92-6; Butyric Acids; Histone Deacetylases, EC 3.5.1.-; Histones; Hydroxamic Acids; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; RNA, Messenger; Tissue Plasminogen Activator, EC 220.127.116.11; Tretinoin, 302-79-4; trichostatin A, 58880-19-6 Subject Biologybutyric acidhistone deacetylasehistone h4tissue plasminogen activatortrichostatin aacetylationarticlecontrolled studydna transcriptionendothelium cellgene expressionhumanhuman cellpriority journalprotein synthesisumbilical veinvascular endotheliumAcetylationButyric AcidButyric AcidsCells, CulturedEndothelium, VascularGene Expression RegulationHistone DeacetylasesHistonesHumanHydroxamic AcidsProto-Oncogene Proteins c-fosProto-Oncogene Proteins c-junRNA, MessengerSupport, Non-U.S. Gov'tTissue Plasminogen ActivatorTranscription, GeneticTretinoin To reference this document use: http://resolver.tudelft.nl/uuid:0f16315a-9b5e-478a-97b4-9383f10255c0 TNO identifier 232896 ISSN 0264-6021 Source Biochemical Journal, 310 (1), 171-176 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.