👤 Masashi Yukawa

3,6-Epidioxy-1,10-bisaboladiene (EDBD), a bisabolane sesquiterpene endoperoxide compound, was previously isolated from Cacalia delphiniifolia and C. hastata in northern Japan. EDBD has cytotoxic effects and induces apoptosis via phosphorylation of p38 mitogen-activated protein kinase in human promyelocytic leukemia HL60 cells. However, the mechanism of action of EDBD has not yet been fully elucidated. In this study, we examined the molecular mechanisms of EDBD in the budding yeast Saccharomyces cerevisiae. EDBD arrested the growth of S. cerevisiae cells by suppressing progression from the G1 phase to the S phase and from the G2 phase to the M phase. Moreover, biochemical and genetic analyses revealed that EDBD activated environmental stress-response pathways involving Hog1 and affected Cln3/G1 cyclin activity, thereby inhibiting the expression of SCB-binding factor and MCB-binding factor target genes. Our results provided important insights into the functions of EDBD in tumor cells and may facilitate the development of EDBD-based antitumor therapies. •Swi4 physically interacts with Swi6 by anti tag coimmunoprecipitation (View interaction). Show less

To determine the significance of anti-U1 RNP antibodies in the cerebrospinal fluid (CSF) of patients with systemic lupus erythematosus (SLE) or mixed connective tissue disease (MCTD) who have central neuropsychiatric SLE (NPSLE). The frequency of antinuclear antibodies including anti-U1 RNP antibodies in the sera and CSF of 24 patients with SLE and 4 patients with MCTD, all of whom had neuropsychiatric syndromes, was determined using an RNA immunoprecipitation assay and an enzyme-linked immunosorbent assay. The frequency of anti-U1 RNP antibodies in the CSF of patients with central NPSLE was examined, and the anti-U1 RNP index ([CSF anti-U1 RNP antibodies/serum anti-U1 RNP antibodies]/[CSF IgG/serum IgG]) was compared with CSF interleukin-6 (IL-6) levels and the albumin quotient (Qalb, an indicator of blood-brain barrier damage). CSF and serum antibodies against U1-70K, U1-A, and U1-C, including autoantigenic regions, were examined, and the U1-70K, U1-A, and U1-C indices as well as the anti-U1 RNP index were calculated. CSF anti-U1 RNP antibodies with an increased anti-U1 RNP index showed 64.3% sensitivity and 92.9% specificity for central NPSLE. The anti-U1 RNP index did not correlate with CSF IL-6 levels or the Qalb. The anti-U1-70K index was higher than the anti-U1-A and anti-U1-C indices in the CSF of anti-U1 RNP antibody-positive patients with central NPSLE. The major autoantigenic region for CSF anti-U1-70K antibodies appeared to be localized in U1-70K amino acid 141-164 residue within the RNA-binding domain. The frequency of anti-U1 RNP antibodies in the CSF and the anti-U1 RNP index are useful indicators of central NPSLE in anti-U1 RNP antibody-positive patients. The predominance of anti-U1-70K antibodies in CSF suggests intrathecal anti-U1 RNP antibody production. Show less