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Hirasawa, K.

Publications and source records attributed to Hirasawa, K..

2 recordsLinked to original sources
bioRxiv2020

Development of Microsatellite Markers for a Soricid Water Shrew Chimarrogale platycephalus, and the Success of Individual Identification Using It.

The soricid water shrew, Chimarrogale platycephalus, is a mammal species endemic to the Japanese Islands. They inhabit the islands of Honshu and Kyushu, and are considered to be extinct in Shikoku. Information on this water shrew from Honshu and Kyushu is also scarce, and C. platycephalus is registered on the Japanese Governments red list as an endangered species. Almost all study areas such as regarding their ethology, ecology, also their phylogenetics are lacking. The delay in these foundational studies is due to difficulties related to them being both nocturnal and aquatic. In order to study of C. platycephalus, it is essential to conduct field research in mountain streams at night under such circumstances. In response to such difficult circumstances, we established a genetic analysis method using the feces of C. platycephalus, and as a result the accumulation of data on their phylogenetic evolution and phylogeography has increased which has improved our understanding of this species. Furthermore in this study, development of microsatellite markers was carried out, and a total of 21 loci marker analyses were performed. In addition, in order to confirm the credibility of these 21 microsatellite markers, as being able to validly differentiate individuals, all markers were examined using the fecal and tissues specimens from verified separately reared individuals (12 individuals) with the known history of having been reared in an aquarium. As a result, it was revealed that if analyses of the 12 loci were possible, individual differentiation with 100% accuracy was possible. The development of microsatellite markers in this study, and the establishment of individual identification methods by means of this will be expected to greatly contribute to future ecological and ethological research, population genetics and biogeographical research of the water shrew, C. platycephalus.

evolutionary biology↗
bioRxiv2020

MEK reduces cancer-specific PpIX accumulation through the RSK-ABCB1 and HIF-1α-FECH axes

The efficacy of aminolevulinic acid (5-ALA)-based photodynamic diagnosis (5-ALA-PDD) and photodynamic therapy (5-ALA-PDT) is dependent on the 5-ALA-induced cancer-specific accumulation of protoporphyrin IX (PpIX). We previously reported that inhibition of oncogenic Ras/MEK increases PpIX accumulation in cancer cells by reducing PpIX efflux through ATP-binding cassette sub-family B member 1 (ABCB1) as well as PpIX conversion to heme by ferrochelatase (FECH). Here, we sought to identify the downstream pathways of Ras/MEK involved in the regulation of PpIX accumulation via ABCB1 and FECH. First, we demonstrated that Ras/MEK activation reduced PpIX accumulation in RasV12-transformed NIH3T3 cells and HRAS transgenic mice. Knockdown of p90 ribosomal S6 kinases (RSK) 2, 3, or 4 increased PpIX accumulation in the RasV12-transformed NIH3T3 cells. Further, treatment with an RSK inhibitor reduced ABCB1 expression and increased PpIX accumulation. Moreover, HIF-1 expression was reduced when the RasV12-transformed NIH3T3 cells were treated with a MEK inhibitor, demonstrating that HIF-1 is a downstream element of MEK. HIF-1 inhibition decreased the activity of FECH and increased PpIX accumulation. Finally, we demonstrated the involvement of RSKs and HIF-1 in the regulation of PpIX accumulation in human cancer cell lines (DLD-1, SNB-75, Hs 578T, and MDA MB 231). These results demonstrate that the RSK-ABCB1 and HIF-1-FECH axes are the downstream pathways of Ras/MEK involved in the regulation of PpIX accumulation.

cancer biology↗