Tan KT et al. (2011) Cell Metab "Insulin/IGF-1 receptor signaling enhances biosynthetic activity and fat mobilization in the initial phase of starvation in adult male C. elegans."

Tan KT, Lee YH, Luo SC, Ho WZ

[Cell Metab, 2011]

Upon nutrient deprivation, cells are thought to suppress biosynthesis but activate catabolic pathways to provide alternative energy sources and nutrients. However, here we provide evidence that in adult male C.elegans, both biosynthesis and degradation activities, including ribosome biogenesis and turnover, are enhanced during early starvation and appear to depend on the availability of intestinal lipid stores. Upon depletion of the intestinal lipids, further food deprivation results in a significant reduction in metabolic activity in the starved male worms. Our data show that adult C.elegans exhibits a two-phase metabolic response to starvation stress: an initial phase with enhanced metabolic activity that rapidly exhausts the lipid stores, followed by a phase withlow metabolic activity, which outlasts the life of fed control worms. DAF-2 insulin/IGF-1 receptor signaling to the RAS pathway is required for the starvation-induced ribosome biogenesis and rapid lipid depletion in the initial phase of starvation.

Ji K et al. (2015) Food Funct "Inhibition effects of tanshinone on the aggregation of -synuclein."

Liu Y, Ji K, Zhao Y, Yang X, Gong H, Huang K, Wang Z, Yu T

[Food Funct, 2015]

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Lewy bodies that are formed by the aggregated -synuclein are a major pathological feature of PD. Salvia miltiorrhiza has been used as food and as a traditional medicine for centuries in China, with tanshinone I (TAN I) and tanshinone IIA (TAN IIA) as its major bioactive ingredients. Here, we investigated the effects of TAN I and TAN IIA on -synuclein aggregation both in vitro and in a transgenic Caenorhabditis elegans PD model (NL5901). We demonstrated that TAN I and TAN IIA inhibited the aggregation of -synuclein as demonstrated by the prolonged lag time and the reduced thioflavin-T fluorescence intensity; TAN I and TAN IIA also disaggregated preformed mature fibrils in vitro. Moreover, the presence of TAN I or TAN IIA affected the secondary structural transformation of -synuclein from unstructured coils to -sheets, and alleviated the membrane disruption caused by aggregated -synuclein in vitro. Besides, the immuno-dot-blot assay indicated that TAN I and TAN IIA reduce the formation of oligomers and fibrils. We further found that TAN I and TAN IIA extended the life span of NL5901, a strain of transgenic C. elegans that expresses human -synuclein, possibly by attenuating the aggregation of -synuclein. Taken together, our results suggested that TAN I and TAN IIA may be explored further as potential candidates for the prevention and treatment of PD.

Chan YW et al. (2009) J Cell Biol "Mitotic control of kinetochore-associated dynein and spindle orientation by human Spindly."

Schmitz MH, Chan YW, Gerlich DW, Nigg EA, Santamaria A, Fava LL, Uldschmid A

[J Cell Biol, 2009]

Mitotic spindle formation and chromosome segregation depend critically on kinetochore-microtubule (KT-MT) interactions. A new protein, termed Spindly in Drosophila and SPDL-1 in C. elegans, was recently shown to regulate KT localization of dynein, but depletion phenotypes revealed striking differences, suggesting evolutionarily diverse roles of mitotic dynein. By characterizing the function of Spindly in human cells, we identify specific functions for KT dynein. We show that localization of human Spindly (hSpindly) to KTs is controlled by the Rod/Zw10/Zwilch (RZZ) complex and Aurora B. hSpindly depletion results in reduced inter-KT tension, unstable KT fibers, an extensive prometaphase delay, and severe chromosome misalignment. Moreover, depletion of hSpindly induces a striking spindle rotation, which can be rescued by co-depletion of dynein. However, in contrast to Drosophila, hSpindly depletion does not abolish the removal of MAD2 and ZW10 from KTs. Collectively, our data reveal hSpindly-mediated dynein functions and highlight a critical role of KT dynein in spindle orientation.

Zhang X et al. (2022) Free Radic Biol Med "Tanshinone IIA loaded chitosan nanoparticles decrease toxicity of β-amyloid peptide in a Caenorhabditis elegans model of Alzheimer's disease"

Zhang X, Chang Y, Du L, Wang J, Zhang L, Wang S, Kang X, Liu Y, Zhao Y, Huang Y

[Free Radic Biol Med, 2022]

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases that characterized by the accumulation of β-amyloid peptide (Aβ). Overexpressions of Aβ could induce oxidative stress that might be a key insult to initiate the cascades of Aβ accumulation. As a result, anti-oxidative stress and attenuating Aβ accumulation might be one promising intervention for AD treatment. Tanshinone IIA (Tan IIA), a major component of lipophilic tanshinones in Danshen, is proven to be effective in several diseases, including AD. Due to the poor solubility in water, the clinical application of Tan IIA was limited. Therefore, a great number of nanoparticles were designed to overcome this issue. In the current study, we choose chitson as delivery carrier to load Tanshinone IIA (CS@Tan IIA) and explore the protective effects of CS@Tan IIA on the CL2006 strain, a transgenic C. elegans of AD model organism. Compared with Tan IIA monomer, CS@Tan IIA could significantly prolong the lifespan and attenuate the AD-like symptoms, including reducing paralysis and the Aβ deposition by inhibiting the oxidative stress. The mechanism study showed that the protection of CS@Tan IIA was attenuated by knockdown of daf-16 gene, but not skn-1. The results indicated that DAF-16/SOD-3 pathway was required in the protective effects of CS@Tan IIA. Besides DAF-16/SOD-3 pathway, the Tan IIA-loaded CS nanoparticles might protect the C. elegans against the AD insults via promoting autophagy. All the results consistently suggested that coating by chitosan could improve the solubility of Tan IIA and effectively enhance the protective effects of Tan IIA on AD, which might provide a potential drug loading approach for the hydrophobic drugs as Tan IIA.

Dahl JL et al. (2011) J Bacteriol "Role of phase variation in the resistance of Myxococcus xanthus fruiting bodies to Caenorhabditis elegans predation."

Ulrich CH, Kroft TL, Dahl JL

[J Bacteriol, 2011]

The phenomenon of phase variation between yellow and tan forms of Myxococcus xanthus has been recognized for several decades, but it is not known what role this variation may play in the ecology of myxobacteria. We confirm an earlier report that tan variants are disproportionately more numerous in the resulting spore population of a M. xanthus fruiting body than the tan vegetative cells that contributed to fruiting body formation. However, we found that tan cells may not require yellow cells for fruiting body formation or starvation-induced sporulation of tan cells. Here we report three differences between the yellow and tan variants that may play important roles in the soil ecology of M. xanthus. Specifically, the yellow variant is more capable of forming biofilms, is more sensitive to lysozyme, and is more resistant to ingestion by bacteriophagous nematodes. We also show that the myxobacterial fruiting body is more resistant to predation by worms than are dispersed M. xanthus cells.

Muir RE et al. (2008) Appl Environ Microbiol "Virulence of Leucobacter chromiireducens subsp. solipictus to Caenorhabditis elegans: characterization of a novel host-pathogen interaction."

Tan MW, Muir RE

[Appl Environ Microbiol, 2008]

We describe the pathogenic interaction between a newly described Gram-positive bacterium Leucobacter chromiireducens subsp. solipictus strain TAN 31504 and the nematode Caenorhabditis elegans. TAN 31504 pathogenesis on C. elegans is exerted primarily through infection of the adult nematode uterus. TAN 31504 enters the uterus through the external vulval opening and the ensuing uterine infection is strongly correlated with a significant reduction in host life span. Young worms can fed and develop on TAN 31504, but not preferably over the standard food source. C. elegans reared on TAN 31504 as the sole food source develop into thin adults with little intestinal fat stores, produce few progeny, and subsequently can not persist on the pathogenic food source. Within 12 h of exposure, adult worms challenged with TAN 31504 alter the expression of a number of C. elegans innate immunity-related genes, including nlp-29, which encodes a neuropeptide-like protein. C. elegans exposed briefly to TAN 31504 develop lethal uterine infections analogous to worms exposed continuously to pathogen, suggesting that mere contact with the pathogen is sufficient for the host to become infected. TAN 31504 produces a robust biofilm and this behavior is speculated to play a role in the virulence exerted on the nematode host. The interaction between TAN 31504 and C. elegans provides a convenient opportunity to study bacterial virulence on nematode tissues other than the intestine and may allow for the discovery of host innate immunity elicited specifically in response to vulval-uterine infection.

Muir RE et al. (2007) Int J Syst Evol Microbiol "Leucobacter chromiireducens subsp. solipictus subsp. nov., a pigmented bacterium isolated from the nematode Caenorhabditis elegans, and emended description of L. chromiireducens."

Muir RE, Tan MW

[Int J Syst Evol Microbiol, 2007]

A yellow-pigmented, Gram-positive, aerobic, non-motile, non-spore-forming, irregular rod-shaped bacterium (strain TAN 31504(T)) was isolated from the bacteriophagous nematode Caenorhabditis elegans. Based on 16S rRNA gene sequence similarity, DNA G+C content of 69.5 mol%, 2,4-diaminobutyric acid in the cell-wall peptidoglycan, major menaquinone MK-11, abundance of anteiso- and iso-fatty acids, polar lipids diphosphatidylglycerol and phosphatidylglycerol and a number of shared biochemical characteristics, strain TAN 31504(T) was placed in the genus Leucobacter. DNA-DNA hybridization comparisons demonstrated a 91 % DNA-DNA relatedness between strain TAN 31504(T) and Leucobacter chromiireducens LMG 22506(T) indicating that these two strains belong to the same species, when the recommended threshold value of 70 % DNA-DNA relatedness for the definition of a bacterial species by the ad hoc committee on reconciliation of approaches to bacterial systematics is considered. Based on distinct differences in morphology, physiology, chemotaxonomic markers and various biochemical characteristics, it is proposed to split the species L. chromiireducens into two novel subspecies, Leucobacter chromiireducens subsp. chromiireducens subsp. nov. (type strain L-1(T)=CIP 108389(T)=LMG 22506(T)) and Leucobacter chromiireducens subsp. solipictus subsp. nov. (type strain TAN 31504(T)=DSM 18340(T)=ATCC BAA-1336(T)).

DuMez-Kornegay RN et al. (2024) PLoS Genet "Kombucha Tea-associated microbes remodel host metabolic pathways to suppress lipid accumulation."

DeLoach WLM, Dowen RH, Morris AJ, Baker LS, DuMez-Kornegay RN

[PLoS Genet, 2024]

The popularity of the ancient, probiotic-rich beverage Kombucha Tea (KT) has surged in part due to its purported health benefits, which include protection against metabolic diseases; however, these claims have not been rigorously tested and the mechanisms underlying host response to the probiotics in KT are unknown. Here, we establish a reproducible method to maintain C. elegans on a diet exclusively consisting of Kombucha Tea-associated microbes (KTM), which mirrors the microbial community found in the fermenting culture. KT microbes robustly colonize the gut of KTM-fed animals and confer normal development and fecundity. Intriguingly, animals consuming KTMs display a marked reduction in total lipid stores and lipid droplet size. We find that the reduced fat accumulation phenotype is not due to impaired nutrient absorption, but rather it is sustained by a programed metabolic response in the intestine of the host. KTM consumption triggers widespread transcriptional changes within core lipid metabolism pathways, including upregulation of a suite of lysosomal lipase genes that are induced during lipophagy. The elevated lysosomal lipase activity, coupled with a decrease in lipid droplet biogenesis, is partially required for the reduction in host lipid content. We propose that KTM consumption stimulates a fasting-like response in the C. elegans intestine by rewiring transcriptional programs to promote lipid utilization. Our results provide mechanistic insight into how the probiotics in Kombucha Tea reshape host metabolism and how this popular beverage may impact human metabolism.

Terskikh A et al. (2000) Science ""Fluorescent timer": protein that changes color with time."

Matz M, Ermakova G, Siebert P, Kim SK, Lukyanov S, Kajava AV, Weissman I, Zaraisky A, Terskikh A, Tan PBO, Fradkov A, Zhao X

[Science, 2000]

We generated a mutant of the red fluorescent protein drFP583. The mutant (E5) changes its fluorescence from green to red over time. The rate of color conversion is independent of protein concentration and therefore can be used to trace time-dependent expression. We used in vivo labeling with E5 to measure expression from the heat shock-dependent promoter in Caenorhabditis elegans and from the Otx-2 promoter in developing Xenopus embryos. Thus, E5 is a "fluorescent timer" that can be used to monitor both activation and down-regulation of target promoters on the whole-organism scale.AD - School of Medicine, Stanford University, Stanford, CA 94305, USA. Alexey.Terskikh@Stanford.eduFAU - Terskikh, AAU - Terskikh AFAU - Fradkov, AAU - Fradkov AFAU - Ermakova, GAU - Ermakova GFAU - Zaraisky, AAU - Zaraisky AFAU - Tan, PAU - Tan PFAU - Kajava, A VAU - Kajava AVFAU - Zhao, XAU - Zhao XFAU - Lukyanov, SAU - Lukyanov SFAU - Matz, MAU - Matz MFAU - Kim, SAU - Kim SFAU - Weissman, IAU - Weissman IFAU - Siebert, PAU - Siebert PLA - engID - 1 RO3 TW01362-01/TW/FICPT - Journal ArticleCY - UNITED STATESTA - ScienceJID - 0404511RN - 0 (Heat-Shock Proteins)RN - 0 (Luminescent Proteins)RN - 0 (Nerve Tissue Proteins)RN - 0 (Otx2 protein)RN - 0 (Trans-Activators)RN - 0 (red fluorescent protein)SB - IM

Asif, Muhammad Zaka et al. (2021) MicroPubl Biol

Van der Gaag, Victoria L., Edison, Arthur S., Muzio, Cole J., Asif, Muhammad Zaka, Nocilla, Kelsey A., Guo, Jane

[MicroPubl Biol, 2021]

1-Hydroxyphenazine (1-HP) is a small molecule produced by Pseudomonas aeruginosa, a bacterium that is used for pathogenesis models in C. elegans (Cezairliyan et al., 2013; Mahajan-Miklos, Tan, Rahme, & Ausubel, 1999). 1-HP is an especially interesting toxin to study as it has been shown to interact with human cells causing ciliary-slowing associated with dyskinesia and ciliostasis (Wilson et al., 1987). Prior research in our lab has shown that this molecule is toxic to C. elegans, with an LD50 between 150 and 200 M, but C. elegans can glycosylate 1-HP, which detoxifies the molecule (Stupp et al., 2013).