메뉴 건너뛰기




Volumn 109, Issue 4, 2010, Pages 731-743

SIRT1, AMP-activated protein kinase phosphorylation and downstream kinases in response to a single bout of sprint exercise: Influence of glucose ingestion

Author keywords

Fatigue; Human; Performance; Signaling; Skeletal muscle; Wingate

Indexed keywords

ACACB PROTEIN, HUMAN; ACETYL COENZYME A CARBOXYLASE; BIOLOGICAL MARKER; GLUCOSE; GUANOSINE TRIPHOSPHATASE ACTIVATING PROTEIN; HEAT SHOCK PROTEIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; INSULIN; LACTIC ACID; PPARGC1A PROTEIN, HUMAN; PRKAA1 PROTEIN, HUMAN; PRKAA2 PROTEIN, HUMAN; PROTEIN KINASE B; SERINE; SIRT1 PROTEIN, HUMAN; SIRTUIN 1; TBC1D4 PROTEIN, HUMAN; THREONINE; TRANSCRIPTION FACTOR; GLUCOSE BLOOD LEVEL;

EID: 77954887503     PISSN: 14396319     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00421-010-1413-y     Document Type: Article
Times cited : (71)

References (63)
  • 1
    • 21344434775 scopus 로고    scopus 로고
    • Diverging regulation of pyruvate dehydrogenase kinase isoform gene expression in cultured human muscle cells
    • Abbot EL, McCormack JG, Reynet C, Hassall DG, Buchan KW, Yeaman SJ (2005) Diverging regulation of pyruvate dehydrogenase kinase isoform gene expression in cultured human muscle cells. FEBS J 272:3004-3014
    • (2005) FEBS J , vol.272 , pp. 3004-3014
    • Abbot, E.L.1    McCormack, J.G.2    Reynet, C.3    Hassall, D.G.4    Buchan, K.W.5    Yeaman, S.J.6
  • 4
    • 33749370466 scopus 로고    scopus 로고
    • Increased malonyl-CoA levels in muscle from obese and type 2 diabetic subjects lead to decreased fatty acid oxidation and increased lipogenesis; Thiazolidinedione treatment reverses these defects
    • Bandyopadhyay GK, Yu JG, Ofrecio J, Olefsky JM (2006) Increased malonyl-CoA levels in muscle from obese and type 2 diabetic subjects lead to decreased fatty acid oxidation and increased lipogenesis; thiazolidinedione treatment reverses these defects. Diabetes 55:2277-2285
    • (2006) Diabetes , vol.55 , pp. 2277-2285
    • Bandyopadhyay, G.K.1    Yu, J.G.2    Ofrecio, J.3    Olefsky, J.M.4
  • 5
    • 0035929337 scopus 로고    scopus 로고
    • Insulin antagonizes AMP-activated protein kinase activation by ischemia or anoxia in rat hearts, without aVecting total adenine nucleotides
    • Beauloye C, Marsin AS, Bertrand L, Krause U, Hardie DG, Vanoverschelde JL, Hue L (2001) Insulin antagonizes AMP-activated protein kinase activation by ischemia or anoxia in rat hearts, without aVecting total adenine nucleotides. FEBS Lett 505:348-352
    • (2001) FEBS Lett , vol.505 , pp. 348-352
    • Beauloye, C.1    Marsin, A.S.2    Bertrand, L.3    Krause, U.4    Hardie, D.G.5    Vanoverschelde, J.L.6    Hue, L.7
  • 6
    • 33845332346 scopus 로고    scopus 로고
    • Predominant alpha2/beta2/gamma3 AMPK activation during exercise in human skeletal muscle
    • Birk JB, Wojtaszewski JF (2006) Predominant alpha2/beta2/gamma3 AMPK activation during exercise in human skeletal muscle. J Physiol 577:1021-1032
    • (2006) J Physiol , vol.577 , pp. 1021-1032
    • Birk, J.B.1    Wojtaszewski, J.F.2
  • 7
    • 0030667467 scopus 로고    scopus 로고
    • Fractional use of anaerobic capacity during a 30- and a 45-s Wingate test
    • Calbet JA, Chavarren J, Dorado C (1997) Fractional use of anaerobic capacity during a 30- and a 45-s Wingate test. Eur J Appl Physiol 76:308-313
    • (1997) Eur J Appl Physiol , vol.76 , pp. 308-313
    • Calbet, J.A.1    Chavarren, J.2    Dorado, C.3
  • 8
    • 12244269097 scopus 로고    scopus 로고
    • Anaerobic energy provision does not limit Wingate exercise performance in endurance-trained cyclists
    • Calbet JA, De Paz JA, Garatachea N, Cabeza de Vaca S, Chavarren J (2003) Anaerobic energy provision does not limit Wingate exercise performance in endurance-trained cyclists. J Appl Physiol 94:668-676
    • (2003) J Appl Physiol , vol.94 , pp. 668-676
    • Calbet, J.A.1    De Paz, J.A.2    Garatachea, N.3    Cabeza De Vaca, S.4    Chavarren, J.5
  • 10
    • 0347318052 scopus 로고    scopus 로고
    • The AMP-activated protein kinase cascade - A unifying system for energy control
    • DOI 10.1016/j.tibs.2003.11.005
    • Carling D (2004) The AMP-activated protein kinase cascade-a unifying system for energy control. Trends Biochem Sci 29:18-24 (Pubitemid 38068476)
    • (2004) Trends in Biochemical Sciences , vol.29 , Issue.1 , pp. 18-24
    • Carling, D.1
  • 11
    • 73449125908 scopus 로고    scopus 로고
    • Relationship between Sirt1 expression and mitochondrial proteins during conditions of chronic muscle use and disuse
    • Chabi B, Adhihetty PJ, O'Leary MF, Menzies KJ, Hood DA (2009) Relationship between Sirt1 expression and mitochondrial proteins during conditions of chronic muscle use and disuse. J Appl Physiol 107:1730-1735
    • (2009) J Appl Physiol , vol.107 , pp. 1730-1735
    • Chabi, B.1    Adhihetty, P.J.2    O'leary, M.F.3    Menzies, K.J.4    Hood, D.A.5
  • 14
    • 0345708301 scopus 로고    scopus 로고
    • Increased insulin receptor signaling and glycogen synthase activity contribute to the synergistic effect of exercise on insulin action
    • Christ-Roberts CY, Pratipanawatr T, Pratipanawatr W, Berria R, Belfort R, Mandarino LJ (2003) Increased insulin receptor signaling and glycogen synthase activity contribute to the synergistic effect of exercise on insulin action. J Appl Physiol 95:2519-2529
    • (2003) J Appl Physiol , vol.95 , pp. 2519-2529
    • Christ-Roberts, C.Y.1    Pratipanawatr, T.2    Pratipanawatr, W.3    Berria, R.4    Belfort, R.5    Mandarino, L.J.6
  • 15
    • 0028068882 scopus 로고
    • PuriWcation of the AMP-activated protein kinase on ATP-gamma-sepharose and analysis of its subunit structure
    • Davies SP, Hawley SA, Woods A, Carling D, Haystead TA, Hardie DG (1994) PuriWcation of the AMP-activated protein kinase on ATP-gamma-sepharose and analysis of its subunit structure. Eur J Biochem 223:351-357
    • (1994) Eur J Biochem , vol.223 , pp. 351-357
    • Davies, S.P.1    Hawley, S.A.2    Woods, A.3    Carling, D.4    Haystead, T.A.5    Hardie, D.G.6
  • 16
    • 0029561919 scopus 로고
    • Studies using bacterially expressed human protein phosphatase-2C alpha and native bovine protein phosphatase-2AC
    • 5'-AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP-activated protein kinase
    • Davies SP, Helps NR, Cohen PT, Hardie DG (1995) 5'-AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP-activated protein kinase. Studies using bacterially expressed human protein phosphatase-2C alpha and native bovine protein phosphatase-2AC. FEBS Lett 377:421-425
    • (1995) FEBS Lett , vol.377 , pp. 421-425
    • Davies, S.P.1    Helps, N.R.2    Cohen, P.T.3    Hardie, D.G.4
  • 18
    • 77950863138 scopus 로고    scopus 로고
    • Increased p70(s6k) phosphorylation during intake of a protein-carbohydrate drink following resistance exercise in the fasted state
    • doi:10.1007/ s00421-009-1289-x
    • Deldicque L, De Bock K, Maris M, Ramaekers M, Nielens H, Francaux M, Hespel P (2009) Increased p70(s6k) phosphorylation during intake of a protein-carbohydrate drink following resistance exercise in the fasted state. Eur J Appl Physiol. doi:10.1007/ s00421-009-1289-x
    • (2009) Eur J Appl Physiol.
    • Deldicque, L.1    De Bock, K.2    Maris, M.3    Ramaekers, M.4    Nielens, H.5    Francaux, M.6    Hespel, P.7
  • 22
    • 0030869792 scopus 로고    scopus 로고
    • Insulin inhibition of 5' adenosine monophosphate-activated protein kinase in the heart results in activation of acetyl coenzyme A carboxylase and inhibition of fatty acid oxidation
    • Gamble J, Lopaschuk GD (1997) Insulin inhibition of 5' adenosine monophosphate-activated protein kinase in the heart results in activation of acetyl coenzyme A carboxylase and inhibition of fatty acid oxidation. Metabolism 46:1270-1274
    • (1997) Metabolism , vol.46 , pp. 1270-1274
    • Gamble, J.1    Lopaschuk, G.D.2
  • 24
    • 64349111923 scopus 로고    scopus 로고
    • Brief intense interval exercise activates AMPK and p38 MAPK signaling and increases the expression of PGC-1alpha in human skeletal muscle
    • Gibala MJ, McGee SL, Garnham AP, Howlett KF, Snow RJ, Hargreaves M (2009) Brief intense interval exercise activates AMPK and p38 MAPK signaling and increases the expression of PGC-1alpha in human skeletal muscle. J Appl Physiol 106:929-934
    • (2009) J Appl Physiol , vol.106 , pp. 929-934
    • Gibala, M.J.1    McGee, S.L.2    Garnham, A.P.3    Howlett, K.F.4    Snow, R.J.5    Hargreaves, M.6
  • 26
    • 65249102660 scopus 로고    scopus 로고
    • The deacetylase enzyme SIRT1 is not associated with oxidative capacity in rat heart and skeletal muscle and its overexpression reduces mitochondrial biogenesis
    • Gurd BJ, Yoshida Y, Lally J, Holloway GP, Bonen A (2009) The deacetylase enzyme SIRT1 is not associated with oxidative capacity in rat heart and skeletal muscle and its overexpression reduces mitochondrial biogenesis. J Physiol 587:1817-1828
    • (2009) J Physiol , vol.587 , pp. 1817-1828
    • Gurd, B.J.1    Yoshida, Y.2    Lally, J.3    Holloway, G.P.4    Bonen, A.5
  • 27
    • 0031717105 scopus 로고    scopus 로고
    • The AMP-activated/SNF1 protein kinase subfamily: Metabolic sensors of the eukaryotic cell?
    • Hardie DG, Carling D, Carlson M (1998) The AMP-activated/SNF1 protein kinase subfamily: metabolic sensors of the eukaryotic cell? Annu Rev Biochem 67:821-855
    • (1998) Annu Rev Biochem , vol.67 , pp. 821-855
    • Hardie, D.G.1    Carling, D.2    Carlson, M.3
  • 28
    • 0038199737 scopus 로고    scopus 로고
    • Management of cellular energy by the AMP-activated protein kinase system
    • Hardie DG, Scott JW, Pan DA, Hudson ER (2003) Management of cellular energy by the AMP-activated protein kinase system. FEBS Lett 546:113-120
    • (2003) FEBS Lett , vol.546 , pp. 113-120
    • Hardie, D.G.1    Scott, J.W.2    Pan, D.A.3    Hudson, E.R.4
  • 29
    • 33745225026 scopus 로고    scopus 로고
    • AMP-activated protein kinase-development of the energy sensor concept
    • Hardie DG, Hawley SA, Scott JW (2006) AMP-activated protein kinase-development of the energy sensor concept. J Physiol 574:7-15
    • (2006) J Physiol , vol.574 , pp. 7-15
    • Hardie, D.G.1    Hawley, S.A.2    Scott, J.W.3
  • 30
    • 0345107247 scopus 로고    scopus 로고
    • Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade
    • Hawley SA, Boudeau J, Reid JL, Mustard KJ, Udd L, Makela TP, Alessi DR, Hardie DG (2003) Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade. J Biol 2:28
    • (2003) J Biol , vol.2 , pp. 28
    • Hawley, S.A.1    Boudeau, J.2    Reid, J.L.3    Mustard, K.J.4    Udd, L.5    Makela, T.P.6    Alessi, D.R.7    Hardie, D.G.8
  • 32
    • 33646828975 scopus 로고    scopus 로고
    • Insulin antagonizes ischemia-induced Thr172 phosphorylation of AMP-activated protein kinase alpha-subunits in heart via hierarchical phosphorylation of Ser485/491
    • Horman S, Vertommen D, Heath R, Neumann D, Mouton V, Woods A, Schlattner U, Wallimann T, Carling D, Hue L, Rider MH (2006) Insulin antagonizes ischemia-induced Thr172 phosphorylation of AMP-activated protein kinase alpha-subunits in heart via hierarchical phosphorylation of Ser485/491. J Biol Chem 281:5335-5340
    • (2006) J Biol Chem , vol.281 , pp. 5335-5340
    • Horman, S.1    Vertommen, D.2    Heath, R.3    Neumann, D.4    Mouton, V.5    Woods, A.6    Schlattner, U.7    Wallimann, T.8    Carling, D.9    Hue, L.10    Rider, M.H.11
  • 34
    • 38949103750 scopus 로고    scopus 로고
    • The effect of exercise and insulin on AS160 phosphorylation and 14-3-3 binding capacity in human skeletal muscle
    • Howlett KF, Mathews A, Garnham A, Sakamoto K (2008) The effect of exercise and insulin on AS160 phosphorylation and 14-3-3 binding capacity in human skeletal muscle. Am J Physiol Endocrinol Metab 294:E401-E407
    • (2008) Am J Physiol Endocrinol Metab , vol.294
    • Howlett, K.F.1    Mathews, A.2    Garnham, A.3    Sakamoto, K.4
  • 35
    • 0345832116 scopus 로고    scopus 로고
    • Knockout of the alpha2 but not alpha1 5'-AMP-activated protein kinase isoform abolishes 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside but not contraction-induced glucose uptake in skeletal muscle
    • Jorgensen SB, Viollet B, Andreelli F, Frosig C, Birk JB, Schjerling P, Vaulont S, Richter EA, Wojtaszewski JF (2004) Knockout of the alpha2 but not alpha1 5'-AMP-activated protein kinase isoform abolishes 5-aminoimidazole-4- carboxamide-1-beta-4-ribofuranoside but not contraction-induced glucose uptake in skeletal muscle. J Biol Chem 279:1070-1079
    • (2004) J Biol Chem , vol.279 , pp. 1070-1079
    • Jorgensen, S.B.1    Viollet, B.2    Andreelli, F.3    Frosig, C.4    Birk, J.B.5    Schjerling, P.6    Vaulont, S.7    Richter, E.A.8    Wojtaszewski, J.F.9
  • 36
    • 0141925771 scopus 로고    scopus 로고
    • Akt activity negatively regulates phosphorylation of AMP-activated protein kinase in the heart
    • Kovacic S, Soltys CL, Barr AJ, Shiojima I, Walsh K, Dyck JR (2003) Akt activity negatively regulates phosphorylation of AMP-activated protein kinase in the heart. J Biol Chem 278:39422-39427
    • (2003) J Biol Chem , vol.278 , pp. 39422-39427
    • Kovacic, S.1    Soltys, C.L.2    Barr, A.J.3    Shiojima, I.4    Walsh, K.5    Dyck, J.R.6
  • 38
    • 53149116286 scopus 로고    scopus 로고
    • Influence of AMP-activated protein kinase and calcineurin on metabolic networks in skeletal muscle
    • Long YC, Zierath JR (2008) Influence of AMP-activated protein kinase and calcineurin on metabolic networks in skeletal muscle. Am J Physiol Endocrinol Metab 295:E545-E552
    • (2008) Am J Physiol Endocrinol Metab , vol.295
    • Long, Y.C.1    Zierath, J.R.2
  • 39
    • 62149130110 scopus 로고    scopus 로고
    • Cellular regulation of SIRT1
    • Milner J (2009) Cellular regulation of SIRT1. Curr Pharm Des 15:39-44
    • (2009) Curr Pharm des , vol.15 , pp. 39-44
    • Milner, J.1
  • 40
    • 0034973952 scopus 로고    scopus 로고
    • Regulation of skeletal muscle ATP catabolism by AMPD1 genotype during sprint exercise in asymptomatic subjects
    • Norman B, Sabina RL, Jansson E (2001) Regulation of skeletal muscle ATP catabolism by AMPD1 genotype during sprint exercise in asymptomatic subjects. J Appl Physiol 91:258-264
    • (2001) J Appl Physiol , vol.91 , pp. 258-264
    • Norman, B.1    Sabina, R.L.2    Jansson, E.3
  • 43
    • 0037326196 scopus 로고    scopus 로고
    • Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): Transcriptional coactivator and metabolic regulator
    • Puigserver P, Spiegelman BM (2003) Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr Rev 24:78-90
    • (2003) Endocr Rev , vol.24 , pp. 78-90
    • Puigserver, P.1    Spiegelman, B.M.2
  • 45
    • 33745185375 scopus 로고    scopus 로고
    • Higher skeletal muscle alpha2AMPK activation and lower energy charge and fat oxidation in men than in women during submaximal exercise
    • RoepstorV C, Thiele M, Hillig T, Pilegaard H, Richter EA, Wojtaszewski JF, Kiens B (2006) Higher skeletal muscle alpha2AMPK activation and lower energy charge and fat oxidation in men than in women during submaximal exercise. J Physiol 574:125-138
    • (2006) J Physiol , vol.574 , pp. 125-138
    • Roepstorv, C.1    Thiele, M.2    Hillig, T.3    Pilegaard, H.4    Richter, E.A.5    Wojtaszewski, J.F.6    Kiens, B.7
  • 46
    • 0030761412 scopus 로고    scopus 로고
    • Phosphocreatine content in single Wbers of human muscle after sustained submaximal exercise
    • Sahlin K, Soderlund K, Tonkonogi M, Hirakoba K (1997) Phosphocreatine content in single Wbers of human muscle after sustained submaximal exercise. Am J Physiol 273:C172-C178
    • (1997) Am J Physiol , vol.273
    • Sahlin, K.1    Soderlund, K.2    Tonkonogi, M.3    Hirakoba, K.4
  • 49
    • 33744937886 scopus 로고    scopus 로고
    • Activation of cardiac AMPactivated protein kinase by LKB1 expression or chemical hypoxia is blunted by increased Akt activity
    • Soltys CL, Kovacic S, Dyck JR (2006) Activation of cardiac AMPactivated protein kinase by LKB1 expression or chemical hypoxia is blunted by increased Akt activity. Am J Physiol Heart Circ Physiol 290:H2472-H2479
    • (2006) Am J Physiol Heart Circ Physiol , vol.290
    • Soltys, C.L.1    Kovacic, S.2    Dyck, J.R.3
  • 52
    • 44949188628 scopus 로고    scopus 로고
    • Endurance exercise increases the SIRT1 and peroxisome proliferator-activated receptor gamma coactivator-1alpha protein expressions in rat skeletal muscle
    • Suwa M, Nakano H, Radak Z, Kumagai S (2008) Endurance exercise increases the SIRT1 and peroxisome proliferator-activated receptor gamma coactivator-1alpha protein expressions in rat skeletal muscle. Metabolism 57:986-998
    • (2008) Metabolism , vol.57 , pp. 986-998
    • Suwa, M.1    Nakano, H.2    Radak, Z.3    Kumagai, S.4
  • 53
    • 0032891637 scopus 로고    scopus 로고
    • Akt kinases and 2-deoxyglucose uptake in rat skeletal muscles in vivo: Study with insulin and exercise
    • Turinsky J, Damrau-Abney A (1999) Akt kinases and 2-deoxyglucose uptake in rat skeletal muscles in vivo: study with insulin and exercise. Am J Physiol 276:R277-R282
    • (1999) Am J Physiol , vol.276
    • Turinsky, J.1    Damrau-Abney, A.2
  • 54
    • 0032055131 scopus 로고    scopus 로고
    • Activation of protein kinase B beta and gamma isoforms by insulin in vivo and by 3-phosphoinositide-dependent protein kinase-1 in vitro: Comparison with protein kinase B alpha
    • Walker KS, Deak M, Paterson A, Hudson K, Cohen P, Alessi DR (1998) Activation of protein kinase B beta and gamma isoforms by insulin in vivo and by 3-phosphoinositide-dependent protein kinase-1 in vitro: comparison with protein kinase B alpha. Biochem J 331(Pt 1):299-308
    • (1998) Biochem J , vol.331 , Issue.PT. 1 , pp. 299-308
    • Walker, K.S.1    Deak, M.2    Paterson, A.3    Hudson, K.4    Cohen, P.5    Alessi, D.R.6
  • 55
    • 48549107440 scopus 로고    scopus 로고
    • Differential effects of resistance and endurance exercise in the fed state on signalling molecule phosphorylation and protein synthesis in human muscle
    • Wilkinson SB, Phillips SM, Atherton PJ, Patel R, Yarasheski KE, Tarnopolsky MA, Rennie MJ (2008) Differential effects of resistance and endurance exercise in the fed state on signalling molecule phosphorylation and protein synthesis in human muscle. J Physiol 586:3701-3717
    • (2008) J Physiol , vol.586 , pp. 3701-3717
    • Wilkinson, S.B.1    Phillips, S.M.2    Atherton, P.J.3    Patel, R.4    Yarasheski, K.E.5    Tarnopolsky, M.A.6    Rennie, M.J.7
  • 56
    • 0026782061 scopus 로고
    • Insulin activation of acetyl-CoA carboxylase accompanied by inhibition of the 5'-AMP-activated protein kinase
    • Witters LA, Kemp BE (1992) Insulin activation of acetyl-CoA carboxylase accompanied by inhibition of the 5'-AMP-activated protein kinase. J Biol Chem 267:2864-2867
    • (1992) J Biol Chem , vol.267 , pp. 2864-2867
    • Witters, L.A.1    Kemp, B.E.2
  • 57
    • 0034306362 scopus 로고    scopus 로고
    • Isoform-specific and exercise intensity-dependent activation of 5'-AMP-activated protein kinase in human skeletal muscle
    • Wojtaszewski JF, Nielsen P, Hansen BF, Richter EA, Kiens B (2000) Isoform-specific and exercise intensity-dependent activation of 5'-AMP-activated protein kinase in human skeletal muscle. J Physiol 528(Pt 1):221-226
    • (2000) J Physiol , vol.528 , Issue.PT. 1 , pp. 221-226
    • Wojtaszewski, J.F.1    Nielsen, P.2    Hansen, B.F.3    Richter, E.A.4    Kiens, B.5
  • 60
    • 0043210478 scopus 로고    scopus 로고
    • IdentiWcation of phosphorylation sites in AMP-activated protein kinase (AMPK) for upstream AMPK kinases and study of their roles by site-directed mutagenesis
    • Woods A, Vertommen D, Neumann D, Turk R, Bayliss J, Schlattner U, Wallimann T, Carling D, Rider MH (2003b) IdentiWcation of phosphorylation sites in AMP-activated protein kinase (AMPK) for upstream AMPK kinases and study of their roles by site-directed mutagenesis. J Biol Chem 278:28434-28442
    • (2003) J Biol Chem , vol.278 , pp. 28434-28442
    • Woods, A.1    Vertommen, D.2    Neumann, D.3    Turk, R.4    Bayliss, J.5    Schlattner, U.6    Wallimann, T.7    Carling, D.8    Rider, M.H.9


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.