title: Yeast Ca(2+)-signal transduction inhibitors isolated from Dominican amber prevent the degranulation of RBL-2H3 cells through the inhibition of Ca(2+)-influx.
abstract: A new norlabdane compound, named kujigamberol has previously been isolated from Kuji amber (but not from Baltic amber) by activity guided fractionation. However, there has been no study of biological compounds in Dominican amber. Biological activities were examined using the hypersensitive mutant yeast (zds1Δ erg3Δ pdr1Δ pdr3Δ) with respect to Ca(2+)-signal transduction, enzymes and rat basophilic leukemia (RBL)-2H3 cells. The structures were elucidated on the basis of spectral analysis including high resolution (HR)-EI-MS, 1D NMR and 2D NMR. Three diterpenoid compounds, 5(10)-halimen-15-oic acid (1), 3-cleroden-15-oic acid (2) and 8-labden-15-oic acid (3), which are different from the bioactive compounds in Kuji and Baltic ambers, were isolated from Dominican amber. They inhibited both calcineurin (CN) (IC50=40.0, 21.2 and 34.2μM) and glycogen synthase kinase-3β (GSK-3β) (IC50=48.9, 43.8 and 41.1μM) which are involved in the growth restored activity against the mutant yeast. The most abundant compound 2 showed inhibitory activity against both degranulation and Ca(2+)-influx in RBL-2H3 cells. The compounds having the growth restoring activity against the mutant yeast have potential as anti-allergic compounds.
authors: Graduate School of Agriculture, Iwate University, Morioka 020-8550, Japan.
authors: Tomomi
authors: T
authors: Abe
authors: Graduate School of Agriculture, Iwate University, Morioka 020-8550, Japan.
authors: Miki
authors: M
authors: Kobayashi
authors: Graduate School of Agriculture, Iwate University, Morioka 020-8550, Japan.
authors: Yusuke
authors: Y
authors: Okawa
authors: Graduate School of Agriculture, Iwate University, Morioka 020-8550, Japan.
authors: Tomoki
authors: T
authors: Inui
authors: Center for Liberal Arts and Sciences, Iwate Medical University, Yahaba 028-3694, Japan.
authors: Jun
authors: J
authors: Yoshida
authors: Center for Liberal Arts and Sciences, Iwate Medical University, Yahaba 028-3694, Japan.
authors: Hironori
authors: H
authors: Higashio
authors: Kuji Kohaku Co. Ltd., Kuji 028-0071, Japan.
authors: Hisao
authors: H
authors: Shinden
authors: The United Graduate School of Agricultural Sciences, Iwate University, Morioka 020-8550, Japan.
authors: Shota
authors: S
authors: Uesugi
authors: RIKEN Center for Sustainable Research Science, Wako 351-0198, Japan.
authors: Hiroyuki
authors: H
authors: Koshino
authors: Graduate School of Agriculture, Iwate University, Morioka 020-8550, Japan; The United Graduate School of Agricultural Sciences, Iwate University, Morioka 020-8550, Japan. Electronic address: kimurak@iwate-u.ac.jp.
authors: Ken-Ichi
authors: K
authors: Kimura
mesh_terms: D018647:Amber / Q000737:chemistry*; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects*; D015550:Cell Degranulation / Q000187:drug effects*; D002460:Cell Line; D004293:Dominican Republic; D008407:Mast Cells / Q000187:drug effects*; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000187:drug effects*
chemical_list: D018647:Amber
keywords: 3-Cleroden-15-oic acid; Calcineurin; Dominican amber; GSK-3β; RBL-2H3 cells; Saccharomyces cerevisiae