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Clausmarin A, Potential Immunosuppressant Revealed by Yeast-Based Assay and Interleukin-2 Production Assay in Jurkat T Cells.
Suauam, Pitipreya; Yingyongnarongkul, Boon-Ek; Palaga, Tanapat; Miyakawa, Tokichi; Yompakdee, Chulee.
Afiliación
  • Suauam P; Department of Microbiology, Faculty of Science, Chulalongkorn University, Phayathai Road, Pathumwan, Bangkok, 10330, Thailand.
  • Yingyongnarongkul BE; Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Ramkhamhaeng Road, Hua Mark, Bangkapi, Bangkok, 10240, Thailand.
  • Palaga T; Department of Microbiology, Faculty of Science, Chulalongkorn University, Phayathai Road, Pathumwan, Bangkok, 10330, Thailand.
  • Miyakawa T; Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashihiroshima, 739-8530, Japan.
  • Yompakdee C; Department of Microbiology, Faculty of Science, Chulalongkorn University, Phayathai Road, Pathumwan, Bangkok, 10330, Thailand.
PLoS One ; 10(8): e0136804, 2015.
Article en En | MEDLINE | ID: mdl-26313553
Small-molecule inhibitors of Ca2+-signaling pathways are of medicinal importance, as exemplified by the immunosuppressants FK506 and cyclosporin A. Using a yeast-based assay devised for the specific detection of Ca2+-signaling inhibitors, clausmarin A, a previously reported terpenoid coumarin, was identified as an active substance. Here, we investigated the likely mechanism of clausmarin A action in yeast and Jurkat T-cells. In the presence of 100 mM CaCl2 in the growth medium of Ca2+-sensitive Δzds1 strain yeast, clausmarin A exhibited a dose-dependent alleviation of various defects due to hyperactivation of Ca2+ signaling, such as growth inhibition, polarized bud growth and G2 phase cell-cycle arrest. Furthermore, clausmarin A inhibited the growth of Δmpk1 (lacking the Mpk1 MAP kinase pathway) but not Δcnb1 (lacking the calcineurin pathway) strain, suggesting that clausmarin A inhibited the calcineurin pathway as presumed from the synthetic lethality of these pathways. Furthermore, clausmarin A alleviated the serious defects of a strain expressing a constitutively active form of calcineurin. In the human Jurkat T-cell line, clausmarin A exhibited a dose-dependent inhibition of IL-2 production and IL-2 gene transcription, as well as an inhibition of NFAT dephosphorylation. The effects of clausmarin A observed in both yeast and Jurkat cells are basically similar to those of FK506. Our study revealed that clausmarin A is an inhibitor of the calcineurin pathway, and that this is probably mediated via inhibition of calcineurin phosphatase activity. As such, clausmarin A is a potential immunosuppressant.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Saccharomyces cerevisiae / Interleucina-2 / Cumarinas / Inmunosupresores Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2015 Tipo del documento: Article País de afiliación: Tailandia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Saccharomyces cerevisiae / Interleucina-2 / Cumarinas / Inmunosupresores Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2015 Tipo del documento: Article País de afiliación: Tailandia Pais de publicación: Estados Unidos