Kim J et al. (2013) Biofactors "A DAF-16/FoxO3a-dependent longevity signal is initiated by antioxidants."

Kim J, Lee TR, Ishihara N

[Biofactors, 2013]

The precise mechanisms of antioxidant-mediated longevity are poorly understood. We show that an antioxidant treatment can extend the lifespan of Caenorhabditis elegans (C. elegans) through the nuclear translocation of the forkhead box O transcription factor (FoxO) homolog DAF-16. This pathway was found to involve 3-phosphoinositide-dependent kinase-1 (PDK-1) and serum- and glucocorticoid-regulated kinase-1 (SGK-1), distinct from the known oxidative stress-mediated mechanism in which FoxO3a translocation is regulated by c-Jun N-terminal kinase (JNK) and mammalian sterile 20-like kinase-1 (MST-1). The differences in the mechanisms of FoxO activation by antioxidants and oxidants result in differences in FoxO phosphorylation and target gene expression. Based on these results, we found that a combination of early antioxidant treatment and late oxidant treatment is most effective for lifespan extension in C. elegans.

Kim J et al. (2021) Nat Commun "Maintenance of quiescent oocytes by noradrenergic signals."

Hyun M, You YJ, Kim J, Hibi M

[Nat Commun, 2021]

All females adopt an evolutionary conserved reproduction strategy; under unfavorable conditions such as scarcity of food or mates, oocytes remain quiescent. However, the signals to maintain oocyte quiescence are largely unknown. Here, we report that in four different species - Caenorhabditis elegans, Caenorhabditis remanei, Drosophila melanogaster, and Danio rerio - octopamine and norepinephrine play an essential role in maintaining oocyte quiescence. In the absence of mates, the oocytes of Caenorhabditis mutants lacking octopamine signaling fail to remain quiescent, but continue to divide and become polyploid. Upon starvation, the egg chambers of D. melanogaster mutants lacking octopamine signaling fail to remain at the previtellogenic stage, but grow to full-grown egg chambers. Upon starvation, D. rerio lacking norepinephrine fails to maintain a quiescent primordial follicle and activates an excessive number of primordial follicles. Our study reveals an evolutionarily conserved function of thenoradrenergic signal in maintaining quiescent oocytes.

Kim J et al. (2019) Front Comput Neurosci "Neural Interactome: Interactive Simulation of a Neuronal System."

Kim J, Leahy W, Shlizerman E

[Front Comput Neurosci, 2019]

Connectivity and biophysical processes determine the functionality of neuronal networks. We, therefore, developed a real-time framework, called Neural Interactome^,, to simultaneously visualize and interact with the structure and dynamics of such networks. Neural Interactome is a cross-platform framework, which combines graph visualization with the simulation of neural dynamics, or experimentally recorded multi neural time series, to allow application of stimuli to neurons to examine network responses. In addition, Neural Interactome supports structural changes, such as disconnection of neurons from the network (ablation feature). Neural dynamics can be explored on a single neuron level (using a zoom feature), back in time (using a review feature), and recorded (using presets feature). The development of the Neural Interactome was guided by generic concepts to be applicable to neuronal networks with different neural connectivity and dynamics. We implement the framework using a model of the nervous system of <i>Caenorhabditis elegans</i> (<i>C. elegans</i>) nematode, a model organism with resolved connectome and neural dynamics. We show that Neural Interactome assists in studying neural response patterns associated with locomotion and other stimuli. In particular, we demonstrate how stimulation and ablation help in identifying neurons that shape particular dynamics. We examine scenarios that were experimentally studied, such as touch response circuit, and explore new scenarios that did not undergo elaborate experimental studies.

Kim J et al. (2019) Nutrients "Worm-Based Alternate Assessment of Probiotic Intervention against Gut Barrier Infection."

Moon Y, Kim J

[Nutrients, 2019]

The epithelial barrier is the frontline defense against enteropathogenic bacteria and nutrition-linked xenobiotic stressors in the alimentary tract. In particular, enteropathogenic <i>Escherichia coli</i> (EPEC) insults the gut barrier and is increasingly implicated in chronic intestinal diseases such as inflammatory bowel disease. For the efficient development of intervention against barrier-linked distress, the present study provided a <i>Caenorhabditis elegans</i>-based assessment instead of extensive preclinical evaluations using mammalian models. In particular, EPEC infected the gut and shortened the lifespan of <i>C. elegans</i>, which was counteracted by colonization of <i>E. coli</i> strain Nissle 1917 (EcN). In addition to the competitive actions of EcN against EPEC, EcN improved the gut barrier integrity of worms via the Zonula occludens ortholog (Zoo-1) induction, which was verified in the murine infection and colitis model. The worm-based assessment provided a crucial methodology and important insights into the potent chronic events in the human gut barrier after the ingestion of probiotic candidates as a mucoactive dietary or therapeutic agent.

Kim J et al. (2014) Opt Express "Real-time integral imaging system for light field microscopy."

Lee B, Jung JH, Jeong Y, Hong K, Kim J

[Opt Express, 2014]

We propose a real-time integral imaging system for light field microscopy systems. To implement a 3D live in-vivo experimental environment for multiple experimentalists, we generate elemental images for an integral imaging system from the captured light field with a light field microscope in real-time. We apply the f-number matching method to generate an elemental image to reconstruct an undistorted 3D image. Our implemented system produces real and orthoscopic 3D images of micro objects in 16 frames per second. We verify the proposed system via experiments using Caenorhabditis elegans.

Kim J et al. (2010) Biomaterials "The effect of TAT conjugated platinum nanoparticles on lifespan in a nematode Caenorhabditis elegans model."

Shirasawa T, Miyamoto Y, Kim J

[Biomaterials, 2010]

We have shown that platinum nanoparticle species (nano-Pt) is a superoxide dismutase/catalase mimetic that scavenges superoxide and hydrogen peroxide. In Caenorhabditis elegans, nano-Pt functions as an effective antioxidant that induces an extension in lifespan and strong resistance against excessive oxidative stress. Our study with C. elegans was the first trial to use nano-Pt as a bio-active substance. However, a high concentration of nano-Pt was required for these survival effects, probably due to limited membrane permeability. Here, we show that the conjugation of nano-Pt with an HIV-1 TAT fusion protein C-terminally linked to a peptide with high affinity for platinum improves internalization, eliciting a similar level of antioxidant effects at one hundredth the concentration of unconjugated nano-Pt. This approach is a potential method to facilitate translocation of bio-active nanoparticles into living organisms and could be a model assay for estimate the effects of antioxidant in living organism.

Kim J et al. (2016) J Biol Chem "NHX-5, an endosomal Na+/H+ exchanger, is associated with metformin action."

Lee I, Min KJ, Hyun M, Ahn J, Lee HY, Kim J, You YJ

[J Biol Chem, 2016]

Diabetes is one of the most impactful diseases worldwide. The most commonly prescribed anti-diabetic drug is metformin. In this study, we identified an endosomal Na+/H+ exchanger (NHE) as a new potential target of metformin from an unbiased screen in C. elegans. The same NHE homolog also exists in flies where it too mediates the effects of metformin. Our results suggest that endosomal NHEs could be a metformin target and provide an insight to revealing a novel mechanism of action of metformin on regulating the endocytic cycle.

Kim J et al. (2010) J Cell Sci "cdc-25.2, a C. elegans ortholog of cdc25, is required to promote oocyte maturation."

Kim J, Shim YH, Kawasaki I

[J Cell Sci, 2010]

Cdc25 is an evolutionarily conserved protein phosphatase that promotes progression through the cell cycle. Some metazoans have multiple isoforms of Cdc25, which have distinct functions and different expression patterns during development. C. elegans has four cdc-25 genes. cdc-25.1 is required for germline mitotic proliferation. To determine if the other members of the cdc-25 family also contribute to regulation of cell division in the germ line, we examined phenotypes of loss-of-function mutants of the other cdc-25 family genes. We found that cdc-25.2 is also essential for germline development. cdc-25.2 homozygous mutant hermaphrodites exhibited sterility as a result of defects in oogenesis: mutant oocytes were arrested as endomitotic oocytes that were not fertilized successfully. Spermatogenesis and male germline development were not affected. Through genetic interaction studies, we found that CDC-25.2 functions upstream of maturation-promoting factor containing CDK-1 and CYB-3 to promote oocyte maturation by counteracting function of WEE-1.3. We propose that cdc-25 family members function as distinct but related cell cycle regulators to control diverse cell cycles in C. elegans germline development.

Kim J et al. (2009) Mol Cells "A mutation of cdc-25.1 causes defects in germ cells but not in somatic tissues in C. elegans."

Shim YH, Strome S, Kim J, Lee AR, Kawasaki I

[Mol Cells, 2009]

By screening C. elegans mutants for severe defects in germline proliferation, we isolated a new loss-of-function allele of cdc-25.1, bn115. bn115 and another previously identified loss-of-function allele nr2036 do not exhibit noticeable cell division defects in the somatic tissues but have reduced numbers of germ cells and are sterile, indicating that cdc-25.1 functions predominantly in the germ line during postembryonic development, and that cdc-25.1 activity is probably not required in somatic lineages during larval development. We analyzed cell division of germ cells and somatic tissues in bn115 homozygotes with germline-specific anti-PGL-1 immunofluorescence and GFP transgenes that express in intestinal cells, in distal tip cells, and in gonadal sheath cells, respectively. We also analyzed the expression pattern of cdc-25.1 with conventional and quantitative RT-PCR. In the presence of three other family members of cdc-25 in C. elegans defects are observed only in the germ line but not in the somatic tissues in cdc-25.1 single mutants, and cdc-25.1 is expressed predominantly, if not exclusively, in the germ line during postembryonic stages. Our findings indicate that the function of cdc-25.1 is unique in the germ line but likely redundant with other members in the soma.

Kim J et al. (2008) Mech Ageing Dev "Effects of a potent antioxidant, platinum nanoparticle, on the lifespan of Caenorhabditis elegans."

Miyamoto Y, Shirasawa T, Kanayama A, Kajita M, Takahashi M, Shimizu T, Kim J

[Mech Ageing Dev, 2008]

We have shown that platinum nanoparticles (nano-Pt) are a superoxide dismutase (SOD)/catalase mimetic. Various data have shown extension of the Caenorhabditis elegans lifespan by antioxidant treatment. The present study was designed to elucidate the survival benefit conferred by nano-Pt, as compared to the well-known SOD/catalase mimetic EUK-8. At 0.5mM, nano-Pt significantly extended the lifespan of wild-type N2 nematodes and at 0.25 and 0.5mM, nano-Pt recovered the shortened lifespan of the mev-1(kn1) mutant, which is due to excessive oxidative stress. In both instances, EUK-8 at 0.05, 0.5, and 5mM did not extend nematode lifespan. Even when 0.4M paraquat was loaded exogenously, nano-Pt (0.1 and 0.5mM) and EUK-8 (0.5 and 5mM) were effective in rescuing worms. Moreover, 0.5mM nano-Pt significantly reduced the accumulation of lipofuscin and ROS induced by paraquat. We measured the in vitro dose-dependent quenching of O(2)(-) and H(2)O(2), indicating that nano-Pt is a more potent SOD/catalase mimetic than EUK-8. Nano-Pt prolonged the worm lifespan, regardless of thermotolerance or dietary restriction. Taken together, nano-Pt has interesting anti-ageing properties.