Trinucleotide Repeat Polymorphisms of Spinal and Bulbar Muscular Atrophy (SBMA) Gene in Asian Populations / 체질인류학회지

I previously reported the PCR-based Spinal and bulbar muscular atrophy (SBMA) region polymorphisms in the three northeast Asian populations (Chinese, Koreans, Japanese) and Caucasians. Here I update this analysis by including the data of the allele distribution in 378 unrelated individuals from four populations in Asia. In this study I investigated PCR-based CAG repeat polymorphism on the SBMA locus among four Asian populations (Mongolian, Evenki, Orochon, Negrito) and performed the statistical analysis on the eight populations including the previously analyzed data. Both statistical analyses of one-way ANOVA (F=3.284, P=0.002) and Kruskal-Wallis test (chi-square=21.542, DF=7, P=0.003) showed remarkable differences in CAG allele distributions among the populations. Post-hoc test showed that the difference between Negritos and Caucasians was especially significant (Scheffe: P=0.042; Bonferroni: P=0.004). Also a significant differences among Northeast Asians, Caucasians and Negritos (Southeast Asian) were detected by these two tests (ANOVA; F=8.132, P.0.000, Kruskal-Wallis; chi-square=16.614, DF=2, P.0.000). Post-hoc test showed that the differences between Negritos and Caucasias was also especially significant (Scheffe: P=0.001; Bonferroni: P=0.000) among these three groups. These data present that the CAG repeat polymorphism of SBMA gene has a useful information for studies of human population genetics.

zVAD-fmk, unlike BocD-fmk, does not inhibit caspase-6 acting on 14-3-3/Bad pathway in apoptosis of p815 mastocytoma cells

In a preliminary study, we found that benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD- fmk), unlike Boc-aspartyl(OMe)-fluoromethylketone (BocD-fmk), at usual dosage could not prevent genistein-induced apoptosis of p815 mastocytoma cells. This study was undertaken to reveal the mechanism underlying the incapability of zVAD-fmk in preventing this type of apoptosis. We observed that 14-3-3 protein level was reduced in genistein-treated cells and that BocD-fmk but not zVAD-fmk prevented the reduction of 14-3-3 protein level and the release of Bad from 14-3-3. We also demonstrated that truncated Bad to Bcl-xL interaction in genistein- treated cells was prevented by BocD-fmk but not by zVAD-fmk treatment. Our data indicate that BocD- fmk, compared to zVAD-fmk, has a certain preference for inhibiting 14-3-3/Bad signalling pathway. We also elucidated that this differential efficacy of BocD-fmk and zVAD-fmk resulted from the different effect in inhibiting caspase-6 and that co-treatment of zVAD-fmk and caspase-6 specific inhibitor substantially prevented genistein-induced apoptosis. Our data shows that caspase-6 plays a role on Bad/14-3-3 pathway in genistein-induced apoptosis of p815 cells, and that the usual dose of zVAD-fmk, in contrast to BocD-fmk, did not prevent caspase-6 acting on 14-3-3/Bad-mediated event.