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[
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.
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[
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.
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[
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.
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[
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.
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[
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)).
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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
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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).
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[
Immunogenetics,
2000]
Toll receptor systems play an important role in our innate immune response to microbial infection (Rock et al. 1998). Studies of related pathways in arthropods (Hoffmann et all. 1999; Imler and Hofmann 2000) have led to key advances in our understanding of these processes. Until recently, however, the possibility that Toll signals may activate both immune and/or developmental pathways in Caenorhabditis elegans has been largely ignored. Early failures to identify Toll receptors or NFB-like transcription factors in the C. elegans genome (Ruvkun and Hobert 1998) let to the assumption that its Toll pathway was inoperable. Therefore, given the paucity of knowledge on innate immune responses for these animals, there was no impetus to develop C. elegans pathogenicity models. Recent database searches, however, have identified components of the elusive C. elegans Toll receptor pathway (Rich et al. 2000; Tan et al. 1999). The existence of a rudimentary immune response is further supported by evidence that antimicrobial peptides are encoded within the C. elegans genome (Tan and Ausubel 2000). In fact, C. elegans is susceptible to infection from several different pathogens, making this genetically tractable invertebrate an attractive model to study host-pathogen interactions. These developments are particularly important for the study of pathogens such as Pseudomonas aeruginosa whose natural hosts include humans. A suitable C. elegans model could, for example, provided a rapid system to screen candidate antibacterial drugs. Consequently, it has now become important to identify and isolate cDNAs for each component of the C. elegans Toll pathway.
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[
Photochem Photobiol,
2019]
Aging, a universal and unique process, occurs both intrinsically (chronological) and extrinsically (photoaging). Ultraviolet-A (UV-A) mediated stress is a growing health hazard to mankind as it is the major cause of photoaging, which could lead to much damage of skin cells and tissues ranging from tan, burn or even cancer. The present study focuses on the role of antioxidants and other natural compounds which have been widely used in oral/ topical applications to combat and delay the effects of photoaging using model nematode Caenorhabditis elegans. Compounds like green tea extract, naringenin and naringin, which are known for their antioxidant properties, were able to extend lifespan and healthspan of the nematode in normal as well as under UV-A mediated stress conditions. Regulation of both the stress responsive genes (
skn-1 and
sir-2.1) and the aging regulating genes (
daf-2 and
age-1) were attributable for these conditions. Interestingly, it was observed that these compounds when combined in equal ratios by weight worked synergistically to combat the aging process. Pronounced synergistic effects were observed during UV-A mediated stress conditions, suggesting that these could be used as potential anti-photoaging compounds which will be of greater significance for health based research.
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[
MicroPubl Biol,
2020]
Sensation of environmental cues and decisions made as a result of processing of specific sensory cues underlies a myriad of behavioral responses that control every-day life decisions and ultimately survival in many organisms. Despite the appreciation that organisms can sense, process, and translate sensory cues into a behavioral response, the neural mechanisms and molecules that mediate these behaviors are still unclear. Neurotransmitters, such as glutamate, have been implicated in a variety of sensory-dependent behavioral responses, including olfaction, nociception, mechanosensation, and gustation (Mugnaini et al., 1984, Wendy et al., 2013, Daghfous et al., 2018). Despite understanding the importance of glutamate signaling in sensation and translation of contextual cues on behavior, the molecular mechanisms underlying how glutamatergic transmission influences sensory behavior is not fully understood. The nematode, C. elegans, is able to sense a variety of sensory cues. These types of sensory-dependent behavioral responses are mediated through olfactory, gustatory, mechanosensory and aerotactic circuits of the worm (Lans and Jansen, 2004, Milward et al., 2011, Bretscher et al., 2011, Kodama-Namba et al., 2013, Ghosh et al., 2017). Odor guided behavior toward attractants, such as, food cues requires neurotransmitters, that include, glutamate (Chalasani et al., 2007, Chalasani et al., 2010). More specifically, once on a food source, wild type N2 hermaphrodites will generally be retained on a food source (Shtonda and Avery, 2006, Milward et al., 2011, Harris et al., 2019). The types, quality, pathogenicity, and perception of food can modulate food recognition, food leaving rates, and overall navigational strategies towards food (Zhang et al., 2005, Shtonda and Avery, 2006; Ollofsson et al., 2014). These types of behaviors are based on detection of environmental cues, including oxygen, metabolites, pheromones, and odors. Food leaving behaviors have been shown to be influenced by a number of neuronal signals (Shtonda and Avery, 2006, Bendesky et al., 2011, Ollofsson et al., 2014, Meisel et al., 2014, Hao et al., 2018).