• Title/Summary/Keyword: Nutrient starvation

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Ebb-and-Flow of Macroautophagy and Chaperone-Mediated Autophagy in Raji Cells Induced by Starvation and Arsenic Trioxide

  • Li, Cai-Li;Wei, Hu-Lai;Chen, Jing;Wang, Bei;Xie, Bei;Fan, Lin-Lan;Li, Lin-Jing
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.14
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    • pp.5715-5719
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    • 2014
  • Autophagy is crucial in the maintenance of homeostasis and regenerated energy of mammalian cells. Macroautophagy and chaperone-mediated autophagy(CMA) are the two best-identified pathways. Recent research has found that in normal cells, decline of macroautophagy is appropriately parallel with activation of CMA. However, whether it is also true in cancer cells has been poorly studied. Here we focused on cross-talk and conversion between macroautophagy and CMA in cultured Burkitt lymphoma Raji cells when facing serum deprivation and exposure to a toxic compound, arsenic trioxide. The results showed that both macroautophagy and CMA were activated sequentially instead of simultaneously in starvation-induced Raji cells, and macroautophagy was quickly activated and peaked during the first hours of nutrition deprivation, and then gradually decreased to near baseline. With nutrient deprivation persisted, CMA progressively increased along with the decline of macroautophagy. On the other hand, in arsenic trioxide-treated Raji cells, macroautophagy activity was also significantly increased, but CMA activity was not rapidly enhanced until macroautophagy was inhibited by 3-methyladenine, an inhibitor. Together, we conclude that cancer cells exhibit differential responses to diverse stressor-induced damage by autophagy. The sequential switch of the first-aider macroautophagy to the homeostasis-stabilizer CMA, whether active or passive, might be conducive to the adaption of cancer cells to miscellaneous intracellular or extracellular stressors. These findings must be helpful to understand the characteristics, compensatory mechanisms and answer modes of different autophagic pathways in cancer cells, which might be very important and promising to the development of potential targeting interventions for cancer therapies via regulation of autophagic pathways.

Roles of YehZ, a Putative Osmoprotectant Transporter, in Tempering Growth of Salmonella enterica serovar Typhimurium

  • Kim, Seul I;Ryu, Sangryeol;Yoon, Hyunjin
    • Journal of Microbiology and Biotechnology
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    • v.23 no.11
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    • pp.1560-1568
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    • 2013
  • Salmonella, a main cause of foodborne diseases, encounters a variety of environmental stresses and overcomes the stresses by multiple resistance strategies. One of the general responses to hyperosmotic stress is to import or produce compatible solutes so that cells maintain fluid balance and protect proteins and lipids from denaturation. The ProP and ProU systems are the main transport systems for compatible solutes. The OsmU system, recently identified as a third osmoprotectant transport system, debilitates excessive growth as well by reducing production of trehalose. We studied a fourth putative osmoprotectant transport system, YehZYXW, with high sequence similarity with the OsmU system. A Salmonella strain lacking YehZ, a predicted substrate-binding protein, did not suffer from hyperosmolarity but rather grew more rapidly than the wild type regardless of glycine betaine, an osmoprotectant, suggesting that the YehZYXW system controls bacterial growth irrespective of transporting glycine betaine. However, the growth advantage of ${\Delta}yehZ$ was not attributable to an increase in OtsBA-mediated trehalose production, which is responsible for the outcompetition of the ${\Delta}osmU$ strain. Overexpressed YehZ in trans was capable of deaccelerating bacterial growth vice versa, supporting a role of YehZ in dampening growth. The expression of yehZ was increased in response to nutrient starvation, acidic pH, and the presence of glycine betaine under hyperosmotic stress. Identifying substrates for YehZ will help decipher the role of the YehZYXW system in regulating bacterial growth in response to environmental cues.

The effects of succinylacetone on synthesis of protoporphyrin IX and cell growth of Myxococcus xanthus (Myxococcus xanthus의 protoporphyrin IX의 합성과 세포 성장에 대한 succinylacetone의 영향)

  • 이병욱
    • Journal of Life Science
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    • v.13 no.6
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    • pp.814-821
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    • 2003
  • Protoporphyrin IX is an intermediate molecule in the heme biosynthetic pathway. Intra- and extracellular concentrations of protoporphyrin IX in the wild type strain, Myxococcus xanthus DK1622 were measured by reverse phase HPLC. The amount of intracellular protoporphyrin IX continuously increased and reached 6.4 picomoles/mg of protein at the stationary phase. Extracellular protoporphyrin IX began to be detected from the mid-exponential phase. The culture supernatant that was collected in the stationary phase contained approximately 3.0 picomoles of proto-porphyrin IX per mg of protein. Spores formed by nutrient depletion contained about 6.5 picomole protoporphyrin IX/mg of protein. The synthesis of protoporphyrin IX and cell growth were strongly inhibited by addition of succinylacetone to a final concentration of $500\muM$. Succinylacetone, however did not appear to interfere developmental processes. Normal developmental behaviors including aggregation and spore formation was achieved even if succinylacetone was added in a medium. Photolysis among cells grown on a starvation medium supplemented with succinylacetone was also observed. These results indicate that protoporphyrin IX may be important to M. ,xanthus vegetative growth, but not critical to development processes.

Stem Cell Properties of Gastric Cancer Stem-Like Cells under Stress Conditions Are Regulated via the c-Fos/UCH-L3/β-Catenin Axis

  • Jae Hyeong Lee;Sang-Ah Park;Il-Geun Park;Bo Kyung Yoon;Jung-Shin Lee;Ji Min Lee
    • Molecules and Cells
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    • v.46 no.8
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    • pp.476-485
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    • 2023
  • Gastric cancer stem-like cells (GCSCs) possess stem cell properties, such as self-renewal and tumorigenicity, which are known to induce high chemoresistance and metastasis. These characteristics of GCSCs are further enhanced by autophagy, worsening the prognosis of patients. Currently, the mechanisms involved in the induction of stemness in GCSCs during autophagy remain unclear. In this study, we compared the cellular responses of GCSCs with those of gastric cancer intestinal cells (GCICs) whose stemness is not induced by autophagy. In response to glucose starvation, the levels of β-catenin and stemness-related genes were upregulated in GCSCs, while the levels of β-catenin declined in GCICs. The pattern of deubiquitinase ubiquitin C-terminal hydrolase-L3 (UCH-L3) expression in GCSCs and GCICs was similar to that of β-catenin expression depending on glucose deprivation. We also observed that inhibition of UCH-L3 activity reduced β-catenin protein levels. The interaction between UCH-L3 and β-catenin proteins was confirmed, and it reduced the ubiquitination of β-catenin. Our results suggest that UCH-L3 induces the stabilization of β-catenin, which is required to promote stemness during autophagy activation. Also, UCH-L3 expression was regulated by c-Fos, and the levels of c-Fos increased in response to autophagy activation. In summary, our findings suggest that the inhibition of UCH-L3 during nutrient deprivation could suppress stress resistance of GCSCs and increase the survival rates of gastric cancer patients.

Effect of Individual versus Group Rearing and Feeding of Different Levels of Milk and Skim Milk on Nutrient Utilization in Crossbred Calves

  • Babu, L.K.;Pandey, H.N.;Sahoo, A.
    • Asian-Australasian Journal of Animal Sciences
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    • v.16 no.10
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    • pp.1455-1459
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    • 2003
  • A $2{\times}3$ factorial design was used to study the impact of rearing systems, individual (I) vs. group (G) and different levels of milk/skim milk feeding (three schedules, F1, F2 and F3) on performance of crossbred (Bos indicus ${\times}$ Bos taurus) calves. Six calves (three from each sex) were taken in each group on the basis of their birth weight. All the calves were fed colostrum for three days and thereafter, were allotted to three different milk feeding schedules (F), i.e. milk fed upto 8 weeks of age (F1), milk upto 4 weeks followed by 50% (F2) and 100% (F3) replacement of milk with skim milk in the next 4 weeks. Calf starter and cereal green fodder were fed ad libitum to all the calves beginning from second week of age. A digestibility trial was conducted at 15th week of age to assess nutrient utilization during postweaning period. The digestibilty of dry matter (DM), organic matter, total carbohydrate, ether extract and crude protein (CP) were nonsignificant between the rearing systems and the feeding schedules. There was significantly higher digestibility of NDF and ADF in G than I and in F3 than F1 and F2. The concentration CP and total digestible nutrients of the diet ranged from 17.18 to 17.75% and 66.32 to 70.14%, respectively. The DM intake (kg/100 kg body weight) ranged from 1.74 to 2.14 kg during 0 to 8 weeks and 3.19 to 3.41 kg during 0 to 14 weeks of age. The effects during postweaning phase (9-14 weeks of age) showed increased performance in group housed calves compared to individually housed ones with a superior average daily gain (590 vs. 443 g) and dry matter intake (1.79 vs. 1.64 kg). Above all, replacement of milk with skim milk at 50% level after 4th week followed by complete removal after 6th week of age (F2) seemed to suit better in coping with immediate energy starvation due to sole feeding of skim milk (F3) and they performed the best under group housed system of rearing.

Performance of Mixed Cropping of Barley and Hairy Vetch as Green Manure Crops for Following Corn Production

  • Shim, Kang Bo;Kim, Min Tae;Kim, Sung Gook;Jung, Kun Ho;Jeon, Weon Tai;Shin, Su Hyun;Lee, Jae Un;Lee, Jong Ki;Kwon, Young Up
    • Korean Journal of Environmental Agriculture
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    • v.37 no.3
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    • pp.160-165
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    • 2018
  • BACKGROUND: Mixed cropping of legume and grass was effective system in view point of providing organic matter and nitrogen or reducing the nitrogen starvation of following crop. The relation of the change of N and P constituents depending on the cropping types and those effects on the growth and nutrient uptake of the following crop were observed. METHODS AND RESULTS: Three cropping types, hairy vetch mono cropping, barley mono cropping, and mixed cropping of hairy vetch and barley were applied. Soil properties, growth characteristics, and nitrogen production of green manure crops were observed. In additions, the effect of cropping types on the growth pattern of corn as the following crop was observed. In the mixed cropping system, creeping type hairy vetch climbed to the erect type barely for light utilization resulting in improvement of light interception rate and higher LAI (Leaf Area Index) than in mono cropping. Mixed cropping showed higher biomass production and soil nitrogen availability among the cropping types, indicating relatively much more nutrient supply and higher yield production of following crop. CONCLUSION: Mixed cropping showed relatively higher LAI (dry matter) mainly because of intense competition for light utilization usually after flowering stage. Mixed cropping also showed relatively higher yield of corn, the following crop rather than other types, mainly due to the more biomass production potential and higher N and P production ability. Therefore, mixed cropping was adaptable method to reduce or replace chemical fertilizer application for environmentally-friendly agriculture.

Molecular Cloning, Characterization and Expression of a Novel Trehalose-6-phosphate Synthase Homologue from Ginkgo biloba

  • Wu, Weisheng;Pang, Yongzhen;Shen, Guo-An;Lu, Jie;Lin, Juan;Wang, Jin;Sun, Xiaofen;Tang, Kexuan
    • BMB Reports
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    • v.39 no.2
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    • pp.158-166
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    • 2006
  • In many organisms, trehalose acts as protective metabolite against harsh environmental stresses, such as freezing, drought, nutrient starvation, heat and salt. Herein a cDNA (designated as GbTPS, GenBank Accession Number AY884150) encoding a trehalose-6-phosphate synthase homologue was isolated and characterized from the living fossil plant, Ginkgo biloba, which is highly tolerant to drought and cold. GbTPS encoded an 868-amino-acid polypeptide with a predicted isoelectric point of 5.83 and molecular mass of 97.9 kD. Amino acid sequence alignment revealed that GbTPS shared high identity with class II trehalose-6-phosphate synthase homologues (67% identical to AtTPS7), but had only 17% and 23% of identity with OstA from Escherichia coli and ScTPS1 from S. cerevisiae, respectively. DNA gel blot analysis indicated that GbTPS belonged to a small multi-gene family. The expression analysis by RT-PCR showed that GbTPS expressed in a tissue-specific manner in G biloba and might involve in leaf development. GbTPS was also found to be induced by a variety of stresses including cold, salt, drought and mannitol.

The Metabolic Effects of FGF21: From Physiology to Pharmacology (생리, 약학적 관점에서 fibroblast growth factor 21 (FGF21)의 대사 효과 고찰)

  • Song, Parkyong
    • Journal of Life Science
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    • v.30 no.7
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    • pp.640-650
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    • 2020
  • Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF protein family which is highly synthesized in the liver, pancreas, and adipose tissue. Depending on the expression tissue, FGF21 uses endo- or paracrine features to regulate several metabolic pathways including glucose metabolism and energy homeostasis. Different physiologically stressful conditions such as starvation, a ketogenic diet, extreme cold, and mitochondrial dysfunction are known to induce FGF21 synthesis in various tissues to exert either adaptive or defensive mechanisms. More specifically, peroxisome proliferator-activated receptor gamma and peroxisome proliferator-activated receptor alpha control FGF21 expression in adipose tissue and liver, respectively. In addition, the pharmacologic administration of FGF21 has been reported to decrease the body weight and improve the insulin sensitivity and lipoprotein profiles of obese mice and type 2 diabetes patients meaning that FGF21 has attracted huge interest as a therapeutic agent for type 2 diabetes, obesity, and non-alcoholic fatty liver disease. However, understanding FGF21 remains complicated due to the paradoxical condition of its tissue-dependent expression. For example, nutrient deprivation largely increases hepatic FGF21 levels whereas adipose tissue-derived FGF21 is increased under feeding condition. This review discusses the issues of interest that have arisen from existing publications, including the tissue-specific function of FGF21 and its action mechanism. We also summarize the current stage of a clinical trial using several FGF21 analogs.

Myxococcus xanthus socD500 mutation causes Sporulation and Induction of two C-signal Specific Genes (Myxococcus xanthus socD500에 의한 포자 형성 및 CsgA신호에 특이적 유전자의 발현에 관한 연구)

  • 이병욱
    • Journal of Life Science
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    • v.13 no.2
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    • pp.184-190
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    • 2003
  • Myxococcus xanthus is a Gram negative, rod-shaped, soil bacterium that displays a social behaviors, and multicellular development upon nutrient deprivation. The csgA gene encoding a cell surface protein is essential for developmental behaviors including rippling, aggregation, fruiting body formation and sporulation. csgA mutants show normal vegetative growth, but lack all these developmental phenotypes. Expression of the CsgA (C-signal) specific genes are eliminated or dramatically reduced in csgA mutants. In order to identify components of C-signal transduction pathway, second site mutations were introduced into csgA mutants and were identified which can fully or partially restore development of csgA mutants (Rhie, H. G. et. al. 1989. J. Bacteriol. 171, 3268-3276). One of such csgA suppressor mutations, socD500 restores only sporulation to csgA mutants at 15$^{\circ}C$. The socD500 mutaion however eliminates the three basic developmental requirements, starvation, high cell density and a solid surface. Only sporulation, not accompanied with fruiting body formation is induced simply by shifting the temperature of vegetatively growing cells from $32^{\circ}C$ to $15^{\circ}C$. Spores induced by socD500 mutation is not as thick as that of wild-type fruiting body. In socD500 genetic background, two of ten C-signal dependent genes, $\Omega$DK4506 and $\Omega$DK4406 are more highly expressed in growing cells at $15^{\circ}C$. These results indicate that the socD500 mutation may be partly involved in the regulation of expression of two C-signal dependent genes and genes for sporulation in this transduction pathway.