• Title/Summary/Keyword: PKM1

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Knockdown of Pyruvate Kinase M Inhibits Cell Growth and Migration by Reducing NF-κB Activity in Triple-Negative Breast Cancer Cells

  • Ma, Chaobing;Zu, Xueyin;Liu, Kangdong;Bode, Ann M.;Dong, Zigang;Liu, Zhenzhen;Kim, Dong Joon
    • Molecules and Cells
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    • v.42 no.9
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    • pp.628-636
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    • 2019
  • Altered genetic features in cancer cells lead to a high rate of aerobic glycolysis and metabolic reprogramming that is essential for increased cancer cell viability and rapid proliferation. Pyruvate kinase muscle (PKM) is a rate-limiting enzyme in the final step of glycolysis. Herein, we report that PKM is a potential therapeutic target in triple-negative breast cancer (TNBC) cells. We found that PKM1 or PKM2 is highly expressed in TNBC tissues or cells. Knockdown of PKM significantly suppressed cell proliferation and migration, and strongly reduced S phase and induced G2 phase cell cycle arrest by reducing phosphorylation of the CDC2 protein in TNBC cells. Additionally, knockdown of PKM significantly suppressed $NF-{\kappa}B$ (nuclear factor kappa-light-chain-enhancer of activated B cells) activity by reducing the phosphorylation of p65 at serine 536, and also decreased the expression of $NF-{\kappa}B$ target genes. Taken together, PKM is a potential target that may have therapeutic implications for TNBC cells.

Induction of Apoptosis in Human Leukemic Cell Lines by Diallyl Disulfide via Modulation of EGFR/ERK/PKM2 Signaling Pathways

  • Luo, Nian;Zhao, Lv-Cui;Shi, Qing-Qiang;Feng, Zi-Qiang;Chen, Di-Long;Li, Jing
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.8
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    • pp.3509-3515
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    • 2015
  • Background: Diallyl disulfide (DADS) may exert potent anticancer action both in vitro and in vivo. Although its effects on cancer are significant, the underlying mechanisms remain unknown. In this study, we sought to elucidate possible links between DADS and pyruvate kinase (PKM2). Materials and Methods: $KG1{\alpha}$, a leukemia cell line highly expressing PKM2 was used with a cell counting kit (CCK)-8 and flow cytometry (FCM) to investigate the effects of DADS. Relationships between PKM2 and DADS associated with phosphorylation of EGFR, ERK1/2 and MEK, were assessed by western blot analysis. Results: In $KG1{\alpha}$ cells highly expressing PKM2, we found that DADS could affect proliferation, apoptosis and EGFR/ERK/PKM2 signaling pathways, abrogating EGF-induced nuclear accumulation of PKM2. Conclusions: These results suggested that DADS suppressed the proliferation of $KG1{\alpha}$ cells, providing evidence that its proapoptotic effects are mediated through the inhibition of EGFR/ERK/PKM2 signaling pathways.

Translocalization of enhanced PKM2 protein into the nucleus induced by cancer upregulated gene 2 confers cancer stem cell-like phenotypes

  • Yawut, Natpaphan;Kaowinn, Sirichat;Cho, Il-Rae;Budluang, Phatcharaporn;Kim, Seonghye;Kim, Suhkmann;Youn, So Eun;Koh, Sang Seok;Chung, Young-Hwa
    • BMB Reports
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    • v.55 no.2
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    • pp.98-103
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    • 2022
  • Increased mRNA levels of cancer upregulated gene (CUG)2 have been detected in many different tumor tissues using Affymetrix microarray. Oncogenic capability of the CUG2 gene has been further reported. However, the mechanism by which CUG2 overexpression promotes cancer stem cell (CSC)-like phenotypes remains unknown. With recent studies showing that pyruvate kinase muscle 2 (PKM2) is overexpressed in clinical tissues from gastric, lung, and cervical cancer patients, we hypothesized that PKM2 might play an important role in CSC-like phenotypes caused by CUG2 overexpression. The present study revealed that PKM2 protein levels and translocation of PKM2 into the nucleus were enhanced in CUG2-overexpressing lung carcinoma A549 and immortalized bronchial BEAS-2B cells than in control cells. Expression levels of c-Myc, CyclinD1, and PKM2 were increased in CUG2-overexpressing cells than in control cells. Furthermore, EGFR and ERK inhibitors as well as suppression of Yap1 and NEK2 expression reduced PKM2 protein levels. Interestingly, knockdown of β-catenin expression failed to reduce PKM2 protein levels. Furthermore, reduction of PKM2 expression with its siRNA hindered CSC-like phenotypes such as faster wound healing, aggressive transwell migration, and increased size/number of sphere formation. The introduction of mutant S37A PKM2-green fluorescence protein (GFP) into cells without ability to move to the nucleus did not confer CSC-like phenotypes, whereas forced expression of wild-type PKM2 promoted such phenotypes. Overall, CUG2-induced increase in the expression of nuclear PKM2 contributes to CSC-like phenotypes by upregulating c-Myc and CyclinD1 as a co-activator.

Effects of dietary palm kernel meal and β-xylanase on productive performance, fatty liver incidence, and excreta characteristics in laying hens

  • Choi, Won Jun;Kim, Jong Hyuk;Kim, Hyun Woo;Kim, Kwan Eung;Kil, Dong Yong
    • Journal of Animal Science and Technology
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    • v.63 no.6
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    • pp.1275-1285
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    • 2021
  • The objective of the present experiment was to investigate the effect of dietary palm kernel meal (PKM) and β-xylanase supplementation on productive performance, egg quality, fatty liver incidence, and excreta characteristics in laying hens. A total of 320 Hy-Line Brown laying hens (33 weeks of age) were allotted to 1 of 4 treatments with 8 replicates in a feeding trial. Each replicate consisted of 10 consecutive cages with 1 hen per cage. The corn-soybean meal-based control diet was prepared. Additional diet was prepared by including 10% of PKM in the control diet with a partial replacement of corn, soybean meal, and animal fat. In addition, 0.025% β-xylanase was supplemented at the expense of celite to those 2 diets to produce 4 treatment diets in a 2 × 2 factorial arrangement. All hens were provided the diet and water ad libitum for 8 weeks. Results indicated no significant interactions between inclusion of dietary PKM and β-xylanase for all measurements; therefore, the main effects were mainly discussed. Hens fed diets containing 10% PKM had greater (p < 0.05) feed intake and yolk color than those fed diets containing no PKM. However, dietary PKM did not influence fatty liver incidence and excreta characteristics. Dietary β-xylanase supplementation had no effects on all measurements, regardless of inclusion of PKM. In conclusion, PKM can be a potential feed ingredient for laying hens at the inclusion of 10% in the diet. It appears that dietary β-xylanase used in the current experiment has little effect on layer productivity, regardless of inclusion of 10% PKM in the diet.

Effects of Operating Variables on Sorption Capacity of CO2 Absorbents for SEWGS Process (SEWGS 공정용 CO2 흡수제들의 흡수능력에 미치는 조업변수들의 영향)

  • Ryu, Ho-Jung;Kim, Hyo-Sung;Lee, Seung-Yong;Lee, Dong-Ho;Kim, Jae-Chang
    • Korean Chemical Engineering Research
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    • v.50 no.6
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    • pp.994-1001
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    • 2012
  • The Effects of operating variables on reactivity of two $CO_2$ absorbents (PKM1-SU and P4-600) for SEWGS process were investigated in a pressurized fluidized bed reactor. For both $CO_2$ absorbents, $CO_2$ sorption capacity decreased as the number of absorption-regeneration cycles increased. PKM1-SU absorbent represented higher $CO_2$ sorption capacity than that of P4-600 absorbent. However, P4-600 absorbent represented better performance than PKM1-SU absorbent from the view points of regeneration temperature and regeneration rate. For PKM1-SU absorbent, $CO_2$ sorption capacity increased as the steam concentration increased. However, $CO_2$ sorption capacity increased initially as the steam concentration increased from 5% to 10%, but maintained thereafter for P4-600 absorbent. For both $CO_2$ absorbents, $CO_2$ sorption capacity increased as the final regeneration temperature increased. For PKM1-SU absorbent, $CO_2$ sorption capacity increased as the pressure increased and the increment tendency was drastic at higher pressure than 15 bar.

The effect of palm kernel meal supplementation in the diet on the growth performance and meat quality of swine, and on the level of odorous compounds and bacterial communities in swine manure

  • Hwang, Ok-Hwa;Lee, Yoo-Kyoung;Cho, Sung-Back;Han, Deug-Woo;Lee, Sang-Ryoung;Kwag, Jeong-Hoon;Park, Sung-Kwon
    • Korean Journal of Agricultural Science
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    • v.43 no.5
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    • pp.777-787
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    • 2016
  • In the present study, we aimed to investigate the effect of dietary supplementation of palm kernel meal (PKM), as a fermentable carbohydrate source, on the growth performance, meat quality, concentration of odorous compound, and changes in bacterial community in swine manure. Swine (average initial body weight of $51.36{\pm}1.02kg$) were fed diet which included three levels of PKM (0, 2 and 4%), and their manure samples were collected from the slurry pit. Growth performance and meat quality were not affected by PKM treatments (p > 0.05). Levels of phenols and indoles were decreased in the 2 and 4% PKM treatments compared to 0% PKM (control; p < 0.05). Especially, compared to the control, the 2% PKM group showed decreased levels of phenols by 35% and indoles by 34%. Among the dominant bacterial genera, the main change in relative abundance occurred in those belonging to the Firmicutes phylum in PKM treatments. Terrisporobacter and Clostridium were decreased in the PKM groups compared to the control. However, the relative abundance of Intestinibacter, AM406061_g, Coprococcus_g2, Phascolarcotobacterium, EF401875_g, Lactobacillus, and Streptococcus were increased in the PKM group compared to control. Taken together, administration of PKM had a beneficial effect on reducing production of odorous compounds in swine manure, possibly by modulating the communities of predominantly carbohydrate-utilizing bacteria in the large intestine of swine.

Effect of Partial Replacement of Soybean Meal with Palm Kernel Meal and Copra Meal on Growth Performance, Nutrient Digestibility and Carcass Characteristics of Finishing Pigs

  • Kim, B.G.;Lee, J.H.;Jung, H.J.;Han, Y.K.;Park, K.M.;Han, In K.
    • Asian-Australasian Journal of Animal Sciences
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    • v.14 no.6
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    • pp.821-830
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    • 2001
  • To study the effects of partial replacement of soybean meal (SBM) with palm kernel meal (PKM) and copra meal (CM) on growth performance, nutrient digestibility and carcass characteristics in finishing pigs, a total of 150 crossbred pigs (Landrace$\times$Duroc$\times$Yorkshire; average $52.11{\pm}1.08kg$ body weight) were alloted to five treatments, in a randomized block design. The treatments included 1) Control: without PKM or CM, 2) PKM2: 2% of palm kernel meal, 3) PKM4: 4% palm kernel meal, 4) CM2: 2% of copra meal, 5) CM4: 4% of copra meal. During the early finishing period (52~74 kg), growth performance was better in CM diets than in PKM diets or control diet, and in overall period (74~100 was lower (p<0.05) in PKM4 diet than the other diets. Nutrient digestibilies of PKM or CM substituted diets showed the tendency to be lower than those of control diet. In the early finishing period, total amino acid digestibilities of PKM and CM diets had the tendency to be lower than control diet, and in the late finishing period, they were lower (p<0.05) than control diet. Carcass length was longer (p<0.05) in the pigs fed 2% CM than in the pigs fed 4% PKM diet, but other carcass characteristics were not different among treatments. Although the dietary C14:0 content affected (p<0.05) on the C14:0 content in the carcass, the inclusion of PKM or CM in the diet did not affect the total saturated fatty acids and unsaturated fatty acids in the backfat of finishing pigs. Although it was not significant, supplementation of CM at the 2% and 4% of control group tended to decrease feed cost per kg weight gain by 2.89 to 1.42%, respectively. In conclusion, copra meal can be a valuable source of protein in the diet for finishing pigs and may replace other protein sources in pig diets to a considerable extent.

Effect of Dietary β-Mannanase Supplementation and Palm Kernel Meal Inclusion on Laying Performance and Egg Quality in 73 Weeks Old Hens

  • Lee, Jun Yeob;Kim, Sang Yun;Lee, Jae Hwan;Lee, Jeong Heon;Ohh, Sang Jip
    • Journal of Animal Science and Technology
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    • v.55 no.2
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    • pp.115-122
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    • 2013
  • This study was conducted to evaluate the effect of dietary ${\beta}$-mannanase supplementation and palm kernel meal (PKM) inclusion (5%) on laying performance, egg quality and nutrient utilizability of laying hens with 73 weeks of age. A total of 240 Lohmann brown laying hens with average 77.5% egg production were randomly allocated with 60 hens per treatment, 4 replicates per treatment and 15 hens per replicate. Experimental design was a completely randomized design with $2{\times}2$ factorial arrangement, with the factors being (1) two levels of PKM (0 vs. 5%) and (2) with or without dietary ${\beta}$-mannanase (480 IU/kg of diet CTCzyme$^{(R)}$) supplementation. All hens were housed in cages ($35cmW{\times}35cmD{\times}40cmH$) with 2 hens per cage for six weeks feeding trial. Laying performance was recorded daily during feeding trial. Egg quality, nutrients utilizability and blood assays were done at the end of feeding trial. Egg production was improved (P<0.05) by both dietary PKM inclusion and ${\beta}$-mannanase combined supplementation. Either ${\beta}$-mannanase or PKM did not affect feed intakes and feed conversion ratio of all diets. Egg weight of hens fed diet containing 5% of PKM had heavier (P<0.05) eggs compared with hens fed without PKM. Albumen height was improved (P<0.05) by dietary mannanase supplementation. Crude fat utilization of 5% PKM diet was higher than that of no PKM diet regardless of ${\beta}$-mannanase supplementation. Both DM and total carbohydrate utilization were decreased (P<0.05) in hens fed 5% PKM diet. Serum IgG and yolk IgY contents of PKM groups were lower (P<0.05) than those of no PKM groups. This result showed that 5% PKM diet, independent of dietary ${\beta}$-mannanase supplementation, was able to improve egg production. In addition, dietary ${\beta}$-mannanase supplementation could be used for improving the albumen height of eggs.

Effect of dietary supplementation of tapioca on growth performance and meat quality in pigs

  • Park, Jae-Won;Cui, Jing-Ai;Lee, Sang-In;Kim, Young-Hwa;Park, Joon-Cheol;Chae, Byung-Jo;Kim, In-Ho
    • Korean Journal of Agricultural Science
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    • v.42 no.4
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    • pp.347-354
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    • 2015
  • This study evaluated whether dietary supplementation of tapioca could alleviate the negative effects of palm kernel meal (PKM) on growth performance and meat quality in growing and finishing pigs. In experiment 1, 120 73-dold crossbred growing pigs [$(Yorkshire{\times}Landrace){\times}Duroc$], with an average body weight of $31.7{\pm}4.5kg$, were used in a 3-week trial. In experiment 2, 120 108-d-old crossbred finishing pigs [$(Yorkshire{\times}Landrace){\times}Duroc$], with an average BW of $52.6{\pm}4.2kg$ were used in a 10-week trial. Treatments were: CON, a corn-soybean meal-based diet; PKM, 8% PKM, and TPKM, 8% PKM and 10% tapioca. No difference was observed in growth performance or meat quality among treatments in growing pigs. In finishing pigs, no difference was observed in growth performance or meat quality among CON and TPKM dietary treatments. Finishing pigs fed PKM decreases in final BW and ADG compared with those fed CON. Meat quality was not affected by dietary treatments. In conclusion, dietary supplementation of tapioca alleviated anti-nutritional effect of PKM on growth performance in growing and finishing pigs. Thus, the PKM with tapioca could be an available alternative energy source to reduce the cost of pig diets.

Production and Properties of Hemicellulases by a Cellulosimicrobium sp. Isolate (Cellulosimicrobium sp. 분리균의 Hemicellulases 생산성과 효소특성)

  • Yoon, Ki-Hong
    • Microbiology and Biotechnology Letters
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    • v.39 no.3
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    • pp.252-258
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    • 2011
  • A bacterial strain capable of hydrolyzing xylan and locust bean gum (LBG) was isolated from farm soil by enrichment culture using mixture of palm kernel meal (PKM) and wheat bran as carbon source. Nucleotide sequence of 16S rDNA amplified from the isolate YB-1107 showed high similarity with those of genus Cellulosimicrobium strains. Xylanase productivity was increased when the Cellulosimicrobium sp. YB-1107 was grown in the presence of wheat bran or oat spelt xylan, while mannanase productivity was increased drastically when grown in the presence of PKM or LBG. Particularly, maximum mannanase and xylanase activities were obtained in the culture filtrate of media containing 0.7% PKM or 1% wheat bran, respectively. Both enzyme activities were produced at stationary growth phase. Mannanase from the culture filtrate showed the highest activity at $55^{\circ}C$ and pH 6.5. Xylanase activity was optimal at $65^{\circ}C$ and pH 5.5. The predominant products resulting from the mannanase or xylanase hydrolysis were oligosaccharides for LBG or xylan, respectively. In addition, the enzymes could hydrolyze wheat bran and rice bran into oligosaccharides.