Biology subjects

Miyawaki, S.

Publications and source records attributed to Miyawaki, S..

3 recordsLinked to original sources

bioRxiv2020

Senescent cell death as an aging resistance mechanism in naked mole-rat

Naked mole-rats (NMRs) are the longest-lived rodents, showing minimal aging phenotypes. An unsolved paradox is that NMRs exhibit low intracellular anti-oxidant defence despite minimal aging. Here, we explained a link between these “contradicting” features by a phenomenon termed “senescent cell death (SCD)”—Senescence induced cell death in NMR cells due to their inherent vulnerability to reactive oxygen species and unique metabolic system. In NMR skin, we observed few senescent cells during aging or after ultraviolet irradiation, suggesting suppression of senescent cell accumulation in NMR tissue. We discovered that senescent NMR-fibroblasts induce SCD through retinoblastoma protein activation accompanied by autophagy dysregulation, increased oxidative damage and accelerated H2O2-releasing metabolic pathways. During senescence, NMR cells showed resistance to metabolic remodelling unlike mice. Our findings provide mechanistic insights into how extraordinary aging resistance is accomplished in NMR. This will contribute to the development of senolytic drugs to regulate age-related diseases.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cell biology↗

bioRxiv2020

Characterization of brown adipose tissue thermogenesis in the naked mole-rat (Heterocephalus glaber), a poikilothermic mammal

The naked mole-rat (NMR) is a poikilothermic mammal that forms eusocial colonies consisting of one breeding queen, several breeding kings, and subordinates. Despite their poikilothermic feature, NMRs possess brown adipose tissue (BAT), which in homeothermic mammals induces thermogenesis in cold environments. However, NMR-BAT thermogenic potential is controversial, and its physiological roles are unknown. Here, we show that NMR-BAT has beta-3 adrenergic receptor (ADRB3)-dependent thermogenic potential, which contributes to thermogenesis in the isolated queen in non-cold environments. NMR-BAT expressed several brown adipocyte marker genes and showed noradrenaline-dependent thermogenic activity in vitro and in vivo. Although our ADRB3 inhibition experiments revealed that NMR-BAT thermogenesis slightly delays the decrease in body temperature in a cold environment, it was insufficient to maintain the body temperatures of the NMRs. In a non-cold environment, NMRs are known to increase their body temperature by a heat-sharing behavior. Interestingly, we found that the body temperatures of NMRs isolated from the colony were also significantly higher than the ambient temperature. We also show that queens, but not subordinates, induce BAT thermogenesis in isolated, non-cold conditions. Our research provides novel insights into the role and mechanism of thermoregulation in this unique poikilothermic mammal.Competing Interest StatementThe authors have declared no competing interest.View Full Text

zoology↗

bioRxiv2019

An alternative nisin A resistance mechanism affects virulence in Staphylococcus aureus

Nisin A is a bacteriocin produced by Lactococcus lactis and is widely used as a food preservative. Staphylococcus aureus has the BraRS-VraDE system providing resistance against low concentrations of nisin A. The BraRS is one of a two-component system that senses nisin A by BraS and finally induces the expression of ABC transporter VraDE by phosphorylated BraR. Previously, we isolated a highly nisin A resistant strain with increased VraDE expression due to a mutation of braRS. In this study, we isolated a BraRS-VraDE-independent, nisin A resistant mutant from S. aureus MW2. These mutants, designated SAN2 (S. aureus nisin resistant) and SAN469, had a mutation in pmtR (MW1875) which encodes a transcriptional regulator responsible for the expression of the pmtA-D operon. As a result, this mutant exhibited a high level of constitutive production of PmtA-D, a transporter responsible for the export of phenol soluble modulin (PSM). We also obtained two pmtA-D overexpressing, nisin A resistant mutants which contained a point mutation in pmtR from other S. aureus strains.\n\nCharacterization of the mutants revealed that they have a decreased susceptibility to human beta defensin-3 and LL37, which are innate immune factors. Additionally, these mutants showed higher hemolytic activity than the MW2 original strain. Furthermore, in a mouse bacteremia model, the SAN2 strain exhibited a lower survival rate than the MW2 original strain. These results indicate that the over expression of pmtA-D due to the pmtR mutation is an alternative nisin A resistance, which also affects virulence in S. aureus.\n\nAuthor SummaryRecently, the emergence of antibiotic resistant bacteria such as MRSA, MDRP and CRE have brought serious problems for chemotherapy in the world. In addition, many antibacterial agents such as disinfectants and food additives are widely used. Therefore, it raises the possibility that bacteria are becoming resistant to all antibacterial agents. In this study, we investigated whether S. aureus become resistant against nisin A, one of the food additives. Finally, we isolated nisin A highly resistant S. aureus strains. Among these strains, we identified that one strain designated as SAN2 showed nisin A resistance by the overproduction of Pmts which were involved in the secretion of virulence factors called PSMs. We identified a mutation of pmtR gene encoding a regulator for pmt genes. SAN2 strain showed the decreased susceptibility to human antimicrobial peptides and the increased hemolytic activity. Finally, SAN2 showed higher lethal activity in mouse bacteremia model. Our study provides new insights into that S. aureus may cause resistance against various antibacterial food additives, together with the altering the virulence.

microbiology↗