Biology subjects

Kage-Nakadai, E.

Publications and source records attributed to Kage-Nakadai, E..

4 recordsLinked to original sources

bioRxiv2024

A nucleic acid prodrug activates mitochondrial respiration and extends lifespan

Mitochondrial dysfunction caused by aging leads to decreased energy metabolism, resulting in functional decline and increased frailty in multiple tissues. Strategies for protecting and activating mitochondria under stressful conditions are required to suppress aging and age-related diseases. However, it is challenging to develop drugs capable of boosting mitochondrial respiration and compensating for the reduced intracellular adenosine triphosphate (ATP) levels. In this study, we developed a prodrug that stimulates the metabolism of intracellular adenine nucleotides (AXP: adenosine monophosphate (AMP), adenosine diphosphate (ADP), and ATP). It enhances AMP-activated protein kinase activity, fatty acid oxidation, oxidative stress resistance, and mitochondrial respiration, thereby increasing the intracellular ATP levels. Furthermore, this prodrug markedly extended the lifespan of Caenorhabditis elegans. AXP-driven stimulation of cellular energy metabolism proposed herein represents a novel geroprotective strategy and paves the way for the development of bioenergetic-molecule therapeutics.

bioengineering↗

bioRxiv2024

Pathogenicity and intestinal barrier disruptive ability of Malassezia furfur in an alternative model host Caenorhabditis elegans is partially alleviated by Lacticaseibacillus rhamnosus

Malassezia furfur is associated with various diseases; however, the mechanisms underlying its pathogenicity remain largely unknown. In the present study, Caenorhabditis elegans was used as the model host to evaluate M. furfur pathogenicity. Additionally, effects of lactic acid bacteria against M. furfur pathogenicity were evaluated. Compared to Escherichia coli OP50 (OP, control), both live and heat-killed M. furfur reduced the lifespan and body size of C. elegans, although heat-killed M. furfur was less effective than live M. furfur in lifespan shortening. Furthermore, unlike heat-killed M. furfur, live M. furfur disrupted the nematode intestinal barrier. nsy-1 and sek-1 loss-of-function mutants were susceptible to M. furfur, suggesting their involvement in the defense against M. furfur infection. Expression of genes involved in host defense and of those coding for C-type lectin domain-containing proteins and antimicrobial peptides was upregulated in M. furfur-infected C. elegans. Lacticaseibacillus rhamnosus (LR) significantly ameliorated lifespan shortening and body size reduction in M. furfur-infected C. elegans and protected against intestinal barrier disruption, suggesting that LR protects nematodes from M. furfur virulence. This study highlights M. furfur pathogenicity and intestinal barrier disruptive ability in C. elegans and suggests that the M. furfur virulence is partially attenuated by LR. ImportanceInfection with Malassezia furfur shortens the lifespan and disrupts the intestinal barrier in the model host C. elegans. The probiotic Lacticaseibacillus rhamnosus (LR) attenuates M. furfur virulence, thus partially protecting the intestinal tract. Signaling of the innate immune response to M. furfur in C. elegans is mediated by nsy-1 and sek-1, suggesting that the expression of genes involved in the biological defense response may be regulated downstream of nsy-1 and sek-1. This study enhances our understanding of the diseases associated with M. furfur and offers insights into potential preventive and therapeutic methods using probiotics.

microbiology↗

bioRxiv2022

High-performance GPCR optogenetics based on molecular properties of animal opsins, MosOpn3 and LamPP

Optogenetics for GPCR signaling is highly valuable but still requires effective and versatile tools with performance evaluation from molecular properties. Here we investigated performance of two animal opsins, mosquito Opn3 (MosOpn3) and lamprey parapinopsin (LamPP) in optical manipulation in vivo by using C. elegans. MosOpn3 introduced in a nociceptor neurons induced avoidance responses light-dependently with a retinal isomer ubiquitously present in every tissue, like ChR2 and unlike canonical vertebrate opsins. Remarkably, the sensitivity is ~7000 times higher than the case of ChR2 in the light-induced behavior. LamPP introduced in motor neurons induced violet light-dependent stop and green light-dependent go, demonstrating color-dependent manipulation of behaviors using LamPP. Furthermore, our molecular engineering extended the usability of MosOpn3 and LamPP to different signaling cascades and kinetics. Current findings demonstrated that the availability of two animal opsins is equivalent to that of ChR2 in terms of retinal requirement, providing solid strategies for GPCR optogenetics.

biochemistry↗

bioRxiv2021

Seroepidemiological survey on pigs and cattle for novel K88 (F4)-like colonization factor detected in human enterotoxigenic Escherichia coli

Enterotoxigenic Escherichia coli (ETEC) strains that express various fimbrial or nonfimbrial colonization factors and enterotoxins are critical causes of diarrheal diseases. Human ETEC serotype O169:H41 (O169) has been a representative of epidemic ETEC worldwide; the organism shows massive adherence to HEp-2 cells similar to enteroaggregative E. coli. Previously, we determined the complete sequence of the unstable virulence plasmid, pEntYN10. The plasmid included a unique set of genes encoding a novel colonization factor (CF) resembling K88 (F4) of porcine ETEC, in addition to CS6, a well-known representative CF of human ETEC, and another novel CF similar to CS8 (CFA/III) of human ETEC. To determine whether the K88-like CF (after this, K88O169) allows the organisms to infect domestic animals like the original K88-harboring strains that can cause diarrhea in piglets, samples were tested for antibodies against recombinant proteins of possible paralogous adhesins, FaeG1 and FaeG2, from K88O169 and the FaeG of typical K88 (F4). The seroepidemiological study using recombinant antigens (two paralogs FaeG1 and FaeG2 from K88O169) showed reactivity of porcine (18.0%) and bovine (17.1%) sera to K88O169 FaeG1 and/or FaeG2 antigens on indirect ELISA tests. These results suggest that E. coli with K88O169 adhesin can infect various hosts, including pigs and cattle. This is the first report of domestic animals having antibodies to K88O169 of human ETEC. Although human ETEC had been thought to be distinguished from those of domestic animals based on colonization factors, zoonotic strains may conceal themselves among human ETEC organisms. The concept of One Health should be adopted to intervene in ETEC infections among animals and humans.

microbiology↗