• 제목/요약/키워드: Protein phosphatase 2A

검색결과 518건 처리시간 0.029초

The Roles of Peroxiredoxin and Thioredoxin in Hydrogen Peroxide Sensing and in Signal Transduction

  • Netto, Luis E.S.;Antunes, Fernando
    • Molecules and Cells
    • /
    • 제39권1호
    • /
    • pp.65-71
    • /
    • 2016
  • A challenge in the redox field is the elucidation of the molecular mechanisms, by which $H_2O_2$ mediates signal transduction in cells. This is relevant since redox pathways are disturbed in some pathologies. The transcription factor OxyR is the $H_2O_2$ sensor in bacteria, whereas Cys-based peroxidases are involved in the perception of this oxidant in eukaryotic cells. Three possible mechanisms may be involved in $H_2O_2$ signaling that are not mutually exclusive. In the simplest pathway, $H_2O_2$ signals through direct oxidation of the signaling protein, such as a phosphatase or a transcription factor. Although signaling proteins are frequently observed in the oxidized state in biological systems, in most cases their direct oxidation by $H_2O_2$ is too slow ($10^1M^{-1}s^{-1}$ range) to outcompete Cys-based peroxidases and glutathione. In some particular cellular compartments (such as vicinity of NADPH oxidases), it is possible that a signaling protein faces extremely high $H_2O_2$ concentrations, making the direct oxidation feasible. Alternatively, high $H_2O_2$ levels can hyperoxidize peroxiredoxins leading to local building up of $H_2O_2$ that then could oxidize a signaling protein (floodgate hypothesis). In a second model, $H_2O_2$ oxidizes Cys-based peroxidases that then through thiol-disulfide reshuffling would transmit the oxidized equivalents to the signaling protein. The third model of signaling is centered on the reducing substrate of Cys-based peroxidases that in most cases is thioredoxin. Is this model, peroxiredoxins would signal by modulating the thioredoxin redox status. More kinetic data is required to allow the identification of the complex network of thiol switches.

단백질 인산화에 의해 매개되는 브라시노스테로이드 신호전달 연구의 최근 상황 (Update on Phosphorylation-Mediated Brassinosteroid Signaling Pathways)

  • 이유;김수환
    • 생명과학회지
    • /
    • 제22권3호
    • /
    • pp.428-436
    • /
    • 2012
  • 단백질 인산화는 세포의 활동을 조절하는 보편적인 과정이다. 브라시노스테로이드(brassinostreoid)에 의해 매개되는 신호전달은 브라시노스테로이드에 의해 활성화된 세포막상의 protein kinase 로부터 인산화되어 있는 전사인자들을 탈인산화하는 연속적인 인산화/탈인산화 과정이다. 브라시노스테로이드에 의해 매개되는 신호전달의 연구는 인산화에 관여하는 kinase 기질상의 아미노산을 밝히고, 그와 관련된 돌연변이체의 표현형을 알아봄으로써 급속하게 발전하였다. BRI1과 BAK1의 자기인산화(autophosphorylation), 상호인산화(transphosphorylation), 타이로신 인산화(tyrosine phosphorylation)를 밝힘으로써 그들의 조절작용을 식물의 생리학적, 발생학적 과정을 더 이해할 수 있는 장이 열렸다. 브라시노스테로이드에 의한 인산화는 수용체에 의해 매개되는 세포 내 함입(endocytosis)과 그에 뒤따르는 수용체의 파괴현상에서도 볼 수 있다. 인산화/탈인산화 과정에 관련하여 브라시노스테로이드에 의해 매개되는 신호전달은 더 연구할 여지가 많이 남아 있다. 이 총설은 단백질의 인산화/탈인산화 과정을 통한 브라시노스테로이드의 신호전달 연구의 최근 상황을 기술하였다.

c-Jun N-terminal Kinase (JNK) induces phosphorylation of amyloid precursor protein (APP) at Thr668, in okadaic acid-induced neurodegeneration

  • Ahn, Ji-Hwan;So, Sang-Pil;Kim, Na-Young;Kim, Hyun-Ju;Yoon, Seung-Yong;Kim, Dong-Hou
    • BMB Reports
    • /
    • 제49권7호
    • /
    • pp.376-381
    • /
    • 2016
  • Several lines of evidence have revealed that phosphorylation of amyloid precursor protein (APP) at Thr668 is involved in the pathogenesis of Alzheimer's disease (AD). Okadaic acid (OA), a protein phosphatase-2A inhibitor, has been used in AD research models to increase tau phosphorylation and induce neuronal death. We previously showed that OA increased levels of APP and induced accumulation of APP in axonal swellings. In this study, we found that in OA-treated neurons, phosphorylation of APP at Thr668 increased and accumulated in axonal swellings by c-jun N-terminal kinase (JNK), and not by Cdk5 or ERK/MAPK. These results suggest that JNK may be one of therapeutic targets for the treatment of AD.

Arabidopsis AHL Gene Encodes a 3'(2'),5'-Bisphosphate Nucleotidase Sensitive to Toxic Heavy Metal Ions

  • Cheong, Jong-Joo;Kwon, Hawk-Bin
    • Journal of Applied Biological Chemistry
    • /
    • 제42권4호
    • /
    • pp.169-174
    • /
    • 1999
  • Arabidopsis AHL gene contains 4 exons encoding a putative protein highly homologous to the yeast salt-sensitive enzyme HAL2, a 3'(2'),5'-bisphosphate nucleotidase involving in reductive sulfate assimilation. AHL cDNA complemented yeast met22 (hal2) mutant. AHL fusion protein expressed in E. coli exhibited $Mg^{2+}$-dependent, 3'-phosphoadenosine 5'-phosphate (PAP)-specific phosphatase activity. $Li^+,\;Na^+,\;K^+$ and $Ca^{2+}$ ions inhibit the enzyme activity by competing with $Mg^{2+}$ for the active site of the enzyme. The enzyme activity was also sensitive to ${\mu}M$ concentrations of toxic heavy metal ions such as $Cd^{2+},\;Cu^{2+}$ and $Zn^{2+}$, but was not recovered by addition of more $Mg^{2+}$ ions, suggesting that these ions inactivate the enzyme with a mechanism other than competition with $Mg^{2+}$ ions. Inhibition of the AHL enzyme activity may result in accumulation of PAP, which is highly toxic to the cell. Thus, the AHL enzyme could be one of the intial targets of heavy metal toxicity in plants.

  • PDF

전기 자극이 치주인대세포와 치은섬유아세포에 미치는 영향 (Effect of the Electrical Stimulation on the Human Periodontal Ligament Cells and Gingival Fibroblasts)

  • 이욱;박준봉;이만섭;권영혁
    • Journal of Periodontal and Implant Science
    • /
    • 제29권4호
    • /
    • pp.821-838
    • /
    • 1999
  • On the basis of the evidences that electrical stimulation could enhance proliferation and differentiation of bone cells and promote healing and regeneration of bone, this study was performed to investigate the effects of electrical stimulation on human periodontal ligament cells and gingival fibroblasts in vitro, which also have important roles in regeneration of periodontium, and to evaluate the potential of clinical application of electrical stimulation. Human periodontal ligament cells and gingival fibroblasts were primarily cultured from the root surface of extracted premolar and the adjacent gingiva without periodontal diseases. In control group, the cells ($5{\times}10^4$ cells/ml)were incubated only in Dulbecco's Modified Eagle's Medium contained with 10% fetal bovine serum. In test groups, electrical stimulation was given at the current intensity of $0.25{\mu]A$(test group 1), $1.0{\mu}A$(test group 2), and $2.5{\mu}A$(test group 3) for 12 hours to the same culture media with the control group. After 12 hour exposure of electrical stimulation, the cells were incubated for 2 and a half days(60 hours), and then each group of cells was analyzed for cell proliferation, protein level, and activity of alkaline phosphatase. The results were as follows ; 1. The Rate of cell proliferation of every test group increased significantly in both periodontal ligament cells and gingival fibroblasts, and in periodontal ligament cells, test group 3 showed significantly increased proliferation compared to the other test groups(p<0.05). 2. In the protein levels, neither periodontal ligament cell nor gingival fibroblast showed statistically significant differences between control and test groups. 3. The activity of alkaline phosphatase in periodontal ligament cells increased significantly in all test groups(p<0.05), but there were no significant differences between 3 test groups. In gingival fibroblasts, the activity of alkaline phosphatase increased significantly only in test group 3(p<0.05). From the above results, it is concluded that electrical stimulation may have beneficial effects on the regeneration of destructed periodontal tissue in regard of the stimulation of periodontal ligament cells and gingival fibroblasts as well as electrically stimulated bone formation that has been known, and that electrical stimulation may have the potential of clinical application.

  • PDF

Blood Biochemical Profile and Rumen Fermentation Pattern of Goats Fed Leaf Meal Mixture or Conventional Cakes as Dietary Protein Supplements

  • Anbarasu, C.;Dutta, Narayan;Sharma, K.;Naulia, Uma
    • Asian-Australasian Journal of Animal Sciences
    • /
    • 제15권5호
    • /
    • pp.665-670
    • /
    • 2002
  • The expediency of replacing cost prohibitive and often inaccessible traditional protein supplements prompted the monitoring of hematological parameters was carried out in female goats at 0, 30, 60 and 90 days post feeding. Rumen environment was (3), respectively fed supplements containing either a leaf meal mixture (LMTM) of Leucaena leucocephala-Morus alba-Tectona grandis (2:1:1) or traditional protein supplements groundnut cake (GNC) or soybean meal (SBM) and wheat straw as basal diet. The periodic monitoring of hematological parameters was carried out in female goats at 0, 30, 60 and 90 days post feeding. Rumen environment was studied in bucks in a $3{\times}3$ switch over design. Rumen liquor was collected at 0, 2, 4, 6 and 8 h post feeding after 4 weeks of feeding. The goats fed on LMTM or GNC had similar dry matter intake (g/kg $W^{0.75}$), which was significantly (p<0.05) higher than SBM. Except for packed cell volume (PCV), none of the blood biochemical constituents (Hemoglobin, serum glucose, total protein, serum albumin (A) and globulin(G), A:G ratio, alkaline phosphatase, transaminases) varied significantly due to replacement of 50% dietary protein by LMTM throughout the experiment. GNC group had significantly higher level of PCV than other treatments. However, the level of serum total protein (p<0.01) tended to increase from 60th day onwards irrespective of dietary treatments. The average rumen pH was significantly higher (p<0.001) on SBM followed by LMTM and GNC, respectively. Total volatile fatty acid (TVFA) production was comparable in goats given LMTM or GNC supplements, the corresponding values were significantly different (p<0.001) when compared with SBM. The ammonical-N, total-N and TCA-precipitable-N (mg/100 ml SRL) did not differ significantly among dietary treatments. It may be concluded that supplementing wheat straw with LMTM based concentrate had no adverse effect on voluntary intake, blood biochemical profile and rumen fermentation pattern of the goats.

Development and Validation of an HPLC-PDA Method for Quantitation of Ten Marker Compounds from Eclipta prostrata (L.) and Evaluation of Their Protein Tyrosine Phosphatase 1B, α-Glucosidase, and Acetylcholinesterase Inhibitory Activities

  • Nguyen, Duc Hung;Le, Duc Dat;Ma, Eun Sook;Min, Byung Sun;Woo, Mi Hee
    • Natural Product Sciences
    • /
    • 제26권4호
    • /
    • pp.326-333
    • /
    • 2020
  • The aerial parts of Eclipta prostrata is used as a traditional medicine and vegetable. In traditional folk medicine, it is used for treatment of hemorrhages, hepatic, disease, renal injuries, hair loss, tooth mobility, and viper bites. In this study, ten compounds (1 - 10) were isolated from the aerial parts of E. prostrata. A reliable high performance liquid chromatography equipped with photometric diode array detector (HPLC-PDA) method was developed to simultaneously quantitate 10 marker compounds [chlorogenic acid (1), paratensein 7-O-��-ᴅ-glucoside (2), quercetin 7-O-��-ᴅ-glucoside (3), luteolin 7-O-��-ᴅ-glucoside (4), apigenin 7-O-��-ᴅ-glucoside (5), apigenin 4'-O-��-ᴅ-glucoside (6), apigenin (7), luteolin (8), wedelolactone (9), and paratensein (10)]. In addition, compounds 5 and 6 showed considerable inhibitory effects against protein-tyrosine phosphatase 1B (PTP1B) enzyme. Moreover, compounds 6 - 8, and 10 exhibited potent α-glucosidase inhibitory effects with IC50 values of 24.5 ± 1.9, 33.0 ± 0.5, 45.5 ± 0.1, and 23.8 ± 1.0 µM, respectively. All compounds (1 - 10) showed considerable acetylcholinesterase (AChE) inhibitory effects with IC50 ranging from 30.1 to 75.2 µM.

Comparison of Protein Electrophoresis Fractions in the Leptospirosis Patient Serum

  • Kim Chong Ho;Park Seung-Taeck;Oh Geum-Ga
    • 대한의생명과학회지
    • /
    • 제10권3호
    • /
    • pp.253-257
    • /
    • 2004
  • The mechanisms by which leptospires caused disease are not well understood. A number of putative virulence factors have been suggested, but with few exceptions their role in pathogenesis remains unclear. In these days, many cases of leptospirosis are diagnosed by serological immunoassay. Leptospirosis is characterized by the histopathology of liver, kidney, heart, and lung, but the electrophoresis fractions of serum protein are not compared. We analyzed total protein, albumin, aspartic aminotranferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatinine and urea nitrogen (UN) in sera of patients diagnosed leptospirosis. Total protein and albumin were decreased in 18.5% and 31.2% of patients, respectively. AST, ALT, ALP, UN and creatinine were increased in 90.4%, 66.9%, 28.0%, 15.9% and 10.8% of patients, respectively. We performed cellulose acetate membrane electrophoresis (EP) on sera of patients increased both of AST and ALT, and of patients increased both of creatinine and UN. In patients increased both of AST and ALT, and in patients increased both of AST and ALT, the relative percentage of albumin to total protein in patient serum was dcreased in 89.1 % of patients. α₁-globulin, α₂-globulin, β-globulin and γ-globulin were increased in 85.1 %, 75.2%, 33.6% and 98.0% of patients, respectively. In patients increased both of creatinine and UN, the relative percentage of albumin to total protein in patient serum was dcreased in 93.8% of patients. α₁-globulin, α₂-globulin, β-globulin and γ-globulin were increased in 87.5%, 100%, 31.2% and 93.8% of patients, respectively. These data indicate that infection of Leptospira causes severe liver damage to most of leptospirosis patients, but doesn't cause renal damage to most of them. The relative rate of serum protein electrophoresis fractions to total protein are not identical with them of typical hepatitis patient.

  • PDF

Swedish mutation within amyloid precursor protein modulates global gene expression towards the pathogenesis of Alzheimer's disease

  • Shin, Jong-Yeon;Yu, Saet-Byeol;Yu, Un-Young;Ahnjo, Sang-Mee;Ahn, Jung-Hyuck
    • BMB Reports
    • /
    • 제43권10호
    • /
    • pp.704-709
    • /
    • 2010
  • The Swedish mutation (K595N/M596L) of amyloid precursor protein (APP-swe) has been known to increase abnormal cleavage of cellular APP by Beta-secretase (BACE), which causes tau protein hyperphosphorylation and early-onset Alzheimer's disease (AD). Here, we analyzed the effect of APP-swe in global gene expression using deep transcriptome sequencing technique. We found 283 genes were down-regulated and 348 genes were up-regulated in APP-swe expressing H4-swe cells compared to H4 wild-type cells from a total of approximately 74 million reads of 38 base pairs from each transcriptome. Two independent mechanisms such as kinase and phosphatase signaling cascades leading hyperphosphorylation of tau protein were regulated by the expression of APP-swe. Expressions of catalytic subunit as well as several regulatory subunits of protein phosphatases 2A were decreased. In contrast, expressions of tau-phosphorylating glycogen synthase kinase $3\beta$(GSK-3$\beta$), cyclin dependent kinase 5 (CDK5), and cAMP-dependent protein kinase A (PKA) catalytic subunit were increased. Moreover, the expression of AD-related Aquaporin 1 and presenilin 2 expression was regulated by APP-swe. Taken together, we propose that the expression of APP-swe modulates global gene expression directed to AD pathogenesis.

우유혈청(乳牛血淸)의 각종(各種) 간기능검사치(간기능검사치)에 관(關)한 연구(硏究) 1. SGOT, SGPT, SALP, Thymol Turbidity, 혈청총단백량(血淸總蛋白量), 혈청(血淸) Albumin, 혈청(血淸) Globulin, A/G 비율(比率), 총(總) Bilirubin 및 총(總) Cholesterol (Investigation of Some Components in Blood Serum of Healthy Dairy Cattle in a Liver Function Test 1. SGOT, SGPT, SALP, Thymol Turbidity, Total Protein, Albumin, Globulin, A/G Ratio, Total Bilirubin and Total Cholesterol)

  • 박남용
    • 대한수의학회지
    • /
    • 제16권2호
    • /
    • pp.131-139
    • /
    • 1976
  • The concentrations of some components of the serum in a liver function test were determined in samples of 74 apparently healthy dairy cattle, imported from foreign countries in Jeonnam district, during the periods of June to September of 1975 and July to August of 1976. The ranges, mean concentrations and activities of the SGOT, SGPT, SALP, thymol turbidity, total protein, serum albumin, serum globulin, A/G ratio, total bilirubin and total cholesterol were investigated in this work. This results obtained in the survey were summarized as follows: 1. The SGOT activities obtained from Holstein cows ranged from 57 to 129 Sigma Frankel units/ml, with a mean of $96.5{\pm}19.38$ S.F. units/ml. 2. The SGPT activities obtained from Holstein cows ranged from 5 to 49 Sigma Frankel units/ml, with a mean of $21.27{\pm}9.52$ S.F units/ml. 3. The alkaline phosphatase activities of serum obtained from Holstein cows ranged from 0.3 to 3.8 Sigma Frankel units/ml, with a mean of $1.88{\pm}0.94$ S.F. units/ml. 4. The thymol turbidity of serum obtained from Holstein cows ranged from 0.2 to 4.4 Shank Hoagland units/ml, with a mean of $1.69{\pm}0.30$ S.H units/ml. 5. The total serum protein values of Holstein cows ranged from 5.9 to 8.6g/100ml with a mean of $7.17{\pm}0.65g/100ml$. 6. The serum albumin values of Holstein cows ranged from 2.5 to 4.3g/100ml with a mean of $3.24{\pm}0.28g/100ml$. 7. The serum globulin values of Holstein cows ranged from 2.9 to 5.8g/100ml with a mean of $4.02{\pm}0.72g/100ml$. 8. The A/G ratio of serum obtained from Holstein cows ranged from 0.5 to 1.0 with a mean of $0.78{\pm}0.12$. 9. The total bilirubin of serum obtained from Holstein cows ranged from 7.2 to 0.8mg/100ml, with a mean of $0.32{\pm}0.11mg/100ml$. 10. The total cholesterol of serum obtained from Holstein cows ranged from 50.5 to 240.6mg/100ml with a mean of $135.70{\pm}57.44mg/100ml$. 11. There was little difference in the concentrations of the various serum components between cow groups by birth countries and total cow group, except for SGOT activities, serum alkaline phosphatase activities, thymol turbidity of the Holstein cows from New Zealand.

  • PDF