메뉴 건너뛰기




Volumn 55, Issue 6, 2014, Pages 297-305

Ca2+ signaling and regulation of fluid secretion in salivary gland acinar cells

Author keywords

Calcium signaling; IP3R; Orai1; Salivary fluid secretion; STIM1; TRPC1

Indexed keywords

CALCIUM CHANNEL; CALCIUM ION; CALCIUM RELEASE ACTIVATED CALCIUM CHANNEL 1; CAVEOLIN 1; CYTOSOL RECEPTOR; INOSITOL 1,4,5 TRISPHOSPHATE RECEPTOR; MEMBRANE RECEPTOR; REGULATOR PROTEIN; STROMAL INTERACTION MOLECULE 1; TRANSIENT RECEPTOR POTENTIAL CHANNEL 1; CALCIUM; MEMBRANE PROTEIN; STIM1 PROTEIN, HUMAN; TRANSIENT RECEPTOR POTENTIAL CHANNEL C; TUMOR PROTEIN;

EID: 84902334505     PISSN: 01434160     EISSN: 15321991     Source Type: Journal    
DOI: 10.1016/j.ceca.2014.02.009     Document Type: Review
Times cited : (71)

References (69)
  • 1
    • 0033973364 scopus 로고    scopus 로고
    • Regulation of calcium in salivary gland secretion
    • Ambudkar I.S. Regulation of calcium in salivary gland secretion. Crit. Rev. Oral Biol. Med. 2000, 11:4-25.
    • (2000) Crit. Rev. Oral Biol. Med. , vol.11 , pp. 4-25
    • Ambudkar, I.S.1
  • 2
    • 15544391158 scopus 로고    scopus 로고
    • Regulation of fluid and electrolyte secretion in salivary gland acinar cells
    • Melvin J.E., Yule D., Shuttleworth T., Begenisich T. Regulation of fluid and electrolyte secretion in salivary gland acinar cells. Annu. Rev. Physiol. 2005, 67:445-469.
    • (2005) Annu. Rev. Physiol. , vol.67 , pp. 445-469
    • Melvin, J.E.1    Yule, D.2    Shuttleworth, T.3    Begenisich, T.4
  • 4
    • 0035026757 scopus 로고    scopus 로고
    • Subtype-specific regulation of inositol 1,4,5-trisphosphate receptors: controlling calcium signals in time and space
    • Yule D.I. Subtype-specific regulation of inositol 1,4,5-trisphosphate receptors: controlling calcium signals in time and space. J. Gen. Physiol. 2001, 117:431-434.
    • (2001) J. Gen. Physiol. , vol.117 , pp. 431-434
    • Yule, D.I.1
  • 5
    • 33750513825 scopus 로고    scopus 로고
    • Calcium signaling complexes in microdomains of polarized secretory cells
    • Kiselyov K., Wang X., Shin D.M., Zang W., Muallem S. Calcium signaling complexes in microdomains of polarized secretory cells. Cell Calcium 2006, 40:451-459.
    • (2006) Cell Calcium , vol.40 , pp. 451-459
    • Kiselyov, K.1    Wang, X.2    Shin, D.M.3    Zang, W.4    Muallem, S.5
  • 6
    • 39549112572 scopus 로고    scopus 로고
    • Polarized calcium signaling in exocrine gland cells
    • Petersen O.H., Tepikin A.V. Polarized calcium signaling in exocrine gland cells. Annu. Rev. Physiol. 2008, 70:273-299.
    • (2008) Annu. Rev. Physiol. , vol.70 , pp. 273-299
    • Petersen, O.H.1    Tepikin, A.V.2
  • 7
    • 84871280934 scopus 로고    scopus 로고
    • Polarization of calcium signaling and fluid secretion in salivary gland cells
    • Ambudkar I.S. Polarization of calcium signaling and fluid secretion in salivary gland cells. Curr. Med. Chem. 2012, 19:5774-5781.
    • (2012) Curr. Med. Chem. , vol.19 , pp. 5774-5781
    • Ambudkar, I.S.1
  • 8
    • 79959910709 scopus 로고    scopus 로고
    • Dissection of calcium signaling events in exocrine secretion
    • Ambudkar I.S. Dissection of calcium signaling events in exocrine secretion. Neurochem. Res. 2011, 36:1212-1221.
    • (2011) Neurochem. Res. , vol.36 , pp. 1212-1221
    • Ambudkar, I.S.1
  • 10
    • 0022559188 scopus 로고
    • Identification of cellular activation mechanisms associated with salivary secretion
    • Putney J.W. Identification of cellular activation mechanisms associated with salivary secretion. Annu. Rev. Physiol. 1986, 48:75-88.
    • (1986) Annu. Rev. Physiol. , vol.48 , pp. 75-88
    • Putney, J.W.1
  • 11
    • 0025609411 scopus 로고
    • Capacitative calcium entry revisited
    • Putney J.W. Capacitative calcium entry revisited. Cell Calcium 1990, 10:611-624.
    • (1990) Cell Calcium , vol.10 , pp. 611-624
    • Putney, J.W.1
  • 12
    • 12644282563 scopus 로고    scopus 로고
    • On the molecular basis and regulation of cellular capacitative calcium entry: roles for Trp proteins
    • Birnbaumer L., Zhu X., Jiang M., et al. On the molecular basis and regulation of cellular capacitative calcium entry: roles for Trp proteins. Proc. Natl. Acad. Sci. U. S. A. 1996, 93:15195-151202.
    • (1996) Proc. Natl. Acad. Sci. U. S. A. , vol.93 , pp. 15195-151202
    • Birnbaumer, L.1    Zhu, X.2    Jiang, M.3
  • 13
    • 33644875032 scopus 로고    scopus 로고
    • The TRP superfamily of cation channels
    • Montell C. The TRP superfamily of cation channels. Sci. STKE 2005, 272:re3.
    • (2005) Sci. STKE , vol.272
    • Montell, C.1
  • 15
    • 0034603150 scopus 로고    scopus 로고
    • Trp1, a candidate protein for the store-operated Ca(2+) influx mechanism in salivary gland cells
    • Liu X., Wang W., Singh B.B., et al. Trp1, a candidate protein for the store-operated Ca(2+) influx mechanism in salivary gland cells. J. Biol. Chem. 2000, 275:3403-3411.
    • (2000) J. Biol. Chem. , vol.275 , pp. 3403-3411
    • Liu, X.1    Wang, W.2    Singh, B.B.3
  • 18
    • 27144515996 scopus 로고    scopus 로고
    • 2+ store to the plasma membrane
    • 2+ store to the plasma membrane. Nature 2005, 437:902-905.
    • (2005) Nature , vol.437 , pp. 902-905
    • Zhang, S.L.1    Yu, Y.2    Roos, J.3
  • 19
    • 33748569838 scopus 로고    scopus 로고
    • 2+ store depletion causes STIM1 to accumulate in ER regions closely associated with the plasma membrane
    • 2+ store depletion causes STIM1 to accumulate in ER regions closely associated with the plasma membrane. J. Cell Biol. 2006, 174:803-813.
    • (2006) J. Cell Biol. , vol.174 , pp. 803-813
    • Wu, M.M.1    Buchanan, J.2    Luik, R.M.3    Lewis, R.S.4
  • 20
    • 77950377028 scopus 로고    scopus 로고
    • Molecular basis of calcium signaling in lymphocytes: STIM and ORAI
    • Hogan P.G., Lewis R.S., Rao A. Molecular basis of calcium signaling in lymphocytes: STIM and ORAI. Annu. Rev. Immunol. 2010, 28:491-533.
    • (2010) Annu. Rev. Immunol. , vol.28 , pp. 491-533
    • Hogan, P.G.1    Lewis, R.S.2    Rao, A.3
  • 21
    • 70349146192 scopus 로고    scopus 로고
    • The molecular physiology of CRAC channels
    • Prakriya M. The molecular physiology of CRAC channels. Immunol. Rev. 2009, 231:88-98.
    • (2009) Immunol. Rev. , vol.231 , pp. 88-98
    • Prakriya, M.1
  • 22
    • 55049099696 scopus 로고    scopus 로고
    • STIM1 gates TRPC channels, but not Orai1, by electrostatic interaction
    • Zeng W., Yuan J.P., Kim M.S., et al. STIM1 gates TRPC channels, but not Orai1, by electrostatic interaction. Mol. Cell 2008, 32:439-444.
    • (2008) Mol. Cell , vol.32 , pp. 439-444
    • Zeng, W.1    Yuan, J.P.2    Kim, M.S.3
  • 24
    • 77952668956 scopus 로고    scopus 로고
    • An endoplasmic reticulum/plasma membrane junction: STIM1/Orai1/TRPCs
    • Lee K.P., Yuan J.P., Hong J.H., So I., Worley P.F., Muallem S. An endoplasmic reticulum/plasma membrane junction: STIM1/Orai1/TRPCs. FEBS Lett. 2010, 584:2022-2027.
    • (2010) FEBS Lett. , vol.584 , pp. 2022-2027
    • Lee, K.P.1    Yuan, J.P.2    Hong, J.H.3    So, I.4    Worley, P.F.5    Muallem, S.6
  • 26
    • 78651094967 scopus 로고    scopus 로고
    • Polarized but differential localization and recruitment of STIM1, Orai1 and TRPC channels in secretory cells
    • Hong J.H., Li Q., Kim M.S., et al. Polarized but differential localization and recruitment of STIM1, Orai1 and TRPC channels in secretory cells. Traffic 2011, 12:232-245.
    • (2011) Traffic , vol.12 , pp. 232-245
    • Hong, J.H.1    Li, Q.2    Kim, M.S.3
  • 27
    • 84868094872 scopus 로고    scopus 로고
    • Distinct contributions of Orai1 and TRPC1 to agonist-induced [Ca(2+)](i) signals determine specificity of Ca(2+)-dependent gene expression
    • Ong H.L., Jang S.I., Ambudkar I.S. Distinct contributions of Orai1 and TRPC1 to agonist-induced [Ca(2+)](i) signals determine specificity of Ca(2+)-dependent gene expression. PLoS ONE 2012, 7:e47146.
    • (2012) PLoS ONE , vol.7
    • Ong, H.L.1    Jang, S.I.2    Ambudkar, I.S.3
  • 28
    • 55249091085 scopus 로고    scopus 로고
    • TMEM16A confers receptor-activated calcium-dependent chloride conductance
    • Yang Y.D., Cho H., Koo J.Y., et al. TMEM16A confers receptor-activated calcium-dependent chloride conductance. Nature 2008, 455:1210-1215.
    • (2008) Nature , vol.455 , pp. 1210-1215
    • Yang, Y.D.1    Cho, H.2    Koo, J.Y.3
  • 29
    • 0032830932 scopus 로고    scopus 로고
    • Targeted disruption of the Nhe1 gene prevents muscarinic agonist-induced up-regulation of Na(+)/H(+) exchange in mouse parotid acinar cells
    • Evans R.L., Bell S.M., Schultheis P.J., Shull G.E., Melvin J.E. Targeted disruption of the Nhe1 gene prevents muscarinic agonist-induced up-regulation of Na(+)/H(+) exchange in mouse parotid acinar cells. J. Biol. Chem. 1999, 274:29025-29030.
    • (1999) J. Biol. Chem. , vol.274 , pp. 29025-29030
    • Evans, R.L.1    Bell, S.M.2    Schultheis, P.J.3    Shull, G.E.4    Melvin, J.E.5
  • 30
    • 0030969679 scopus 로고    scopus 로고
    • Upregulation of Na(+)-K(+)-2Cl- cotransporter activity in rat parotid acinar cells by muscarinic stimulation
    • Evans R.L., Turner R.J. Upregulation of Na(+)-K(+)-2Cl- cotransporter activity in rat parotid acinar cells by muscarinic stimulation. J. Physiol. 1997, 499:351-359.
    • (1997) J. Physiol. , vol.499 , pp. 351-359
    • Evans, R.L.1    Turner, R.J.2
  • 31
    • 1642457355 scopus 로고    scopus 로고
    • Cl(-)/HCO(3)(-) exchange is acetazolamide sensitive and activated by a muscarinic receptor-induced [Ca(2+)](i) increase in salivary acinar cells
    • Nguyen H.V., Stuart-Tilley A., Alper S.L., Melvin J.E. Cl(-)/HCO(3)(-) exchange is acetazolamide sensitive and activated by a muscarinic receptor-induced [Ca(2+)](i) increase in salivary acinar cells. Am. J. Physiol. Gastrointest. Liver Physiol. 2004, 286:312-320.
    • (2004) Am. J. Physiol. Gastrointest. Liver Physiol. , vol.286 , pp. 312-320
    • Nguyen, H.V.1    Stuart-Tilley, A.2    Alper, S.L.3    Melvin, J.E.4
  • 32
    • 0025253346 scopus 로고
    • + exchange in rat parotid acinar cells is dependent on calcium but not on protein kinase C
    • + exchange in rat parotid acinar cells is dependent on calcium but not on protein kinase C. J. Biol. Chem. 1990, 265:4284-4289.
    • (1990) J. Biol. Chem. , vol.265 , pp. 4284-4289
    • Manganel, M.1    Turner, R.J.2
  • 34
    • 30344474272 scopus 로고    scopus 로고
    • 2+ signaling microdomains:platforms for the assembly and regulation of TRPC channels
    • 2+ signaling microdomains:platforms for the assembly and regulation of TRPC channels. Trends Pharmacol. Sci. 2006, 27:25-32.
    • (2006) Trends Pharmacol. Sci. , vol.27 , pp. 25-32
    • Ambudkar, I.S.1
  • 36
    • 4344605231 scopus 로고    scopus 로고
    • M(3) muscarinic acetylcholine receptor plays a critical role in parasympathetic control of salivation in mice
    • Nakamura T., Matsui M., Uchida K., et al. M(3) muscarinic acetylcholine receptor plays a critical role in parasympathetic control of salivation in mice. J. Physiol. 2004, 558:561-575.
    • (2004) J. Physiol. , vol.558 , pp. 561-575
    • Nakamura, T.1    Matsui, M.2    Uchida, K.3
  • 37
    • 3342880696 scopus 로고    scopus 로고
    • Cholinergic stimulation of salivary secretion studied with M1 and M3 muscarinic receptor single- and double-knockout mice
    • Gautam D., Heard T.S., Cui Y., Miller G., Bloodworth L., Wess J. Cholinergic stimulation of salivary secretion studied with M1 and M3 muscarinic receptor single- and double-knockout mice. Mol. Pharmacol. 2004, 66:260-267.
    • (2004) Mol. Pharmacol. , vol.66 , pp. 260-267
    • Gautam, D.1    Heard, T.S.2    Cui, Y.3    Miller, G.4    Bloodworth, L.5    Wess, J.6
  • 38
    • 84857501714 scopus 로고    scopus 로고
    • 2+ channel and its cellular function
    • 2+ channel and its cellular function. Biochem. Soc. Symp. 2007, 74:9-22.
    • (2007) Biochem. Soc. Symp. , vol.74 , pp. 9-22
    • Mikoshiba, K.1
  • 39
    • 25844462280 scopus 로고    scopus 로고
    • IP3 receptor types 2 and 3 mediate exocrine secretion underlying energy metabolism
    • Futatsugi A., Nakamura T., Yamada M.K., et al. IP3 receptor types 2 and 3 mediate exocrine secretion underlying energy metabolism. Science 2005, 309:2232-2234.
    • (2005) Science , vol.309 , pp. 2232-2234
    • Futatsugi, A.1    Nakamura, T.2    Yamada, M.K.3
  • 40
    • 84879492181 scopus 로고    scopus 로고
    • Irbit mediates synergy between Ca(2+) and cAMP signaling pathways during epithelial transport in mice
    • Park S., Shcheynikov N., Hong J.H. Irbit mediates synergy between Ca(2+) and cAMP signaling pathways during epithelial transport in mice. Gastroenterology 2013, 145:232-241.
    • (2013) Gastroenterology , vol.145 , pp. 232-241
    • Park, S.1    Shcheynikov, N.2    Hong, J.H.3
  • 41
    • 61749090806 scopus 로고    scopus 로고
    • - secretion by stimulating the transporters pNBC1 and CFTR in the murine pancreatic duct
    • - secretion by stimulating the transporters pNBC1 and CFTR in the murine pancreatic duct. J. Clin. Invest. 2009, 119:193-202.
    • (2009) J. Clin. Invest. , vol.119 , pp. 193-202
    • Yang, D.1    Shcheynikov, N.2    Zeng, W.3
  • 43
    • 0033151932 scopus 로고    scopus 로고
    • Ryanodine and inositol trisphosphate receptors are differentially distributed and expressed in rat parotid gland
    • Zhang X., Wen J., Bidasee K.R., et al. Ryanodine and inositol trisphosphate receptors are differentially distributed and expressed in rat parotid gland. Biochem. J. 1999, 340:519-527.
    • (1999) Biochem. J. , vol.340 , pp. 519-527
    • Zhang, X.1    Wen, J.2    Bidasee, K.R.3
  • 44
    • 79959890527 scopus 로고    scopus 로고
    • The physiological function of store-operated calcium entry
    • Putney J.W. The physiological function of store-operated calcium entry. Neurochem. Res. 2011, 36:1157-1165.
    • (2011) Neurochem. Res. , vol.36 , pp. 1157-1165
    • Putney, J.W.1
  • 45
    • 33847026434 scopus 로고    scopus 로고
    • TRPC1: a core component of store-operated calcium channels
    • Ambudkar I.S. TRPC1: a core component of store-operated calcium channels. Biochem. Soc. Trans. 2007, 35:96-100.
    • (2007) Biochem. Soc. Trans. , vol.35 , pp. 96-100
    • Ambudkar, I.S.1
  • 46
    • 34447281272 scopus 로고    scopus 로고
    • TRPC1: the link between functionally distinct store-operated calcium channels
    • Ambudkar I.S., Ong H.L., Liu X., Bandyopadhyay B.C., Cheng K.T. TRPC1: the link between functionally distinct store-operated calcium channels. Cell Calcium 2007, 42:213-223.
    • (2007) Cell Calcium , vol.42 , pp. 213-223
    • Ambudkar, I.S.1    Ong, H.L.2    Liu, X.3    Bandyopadhyay, B.C.4    Cheng, K.T.5
  • 47
    • 34247898911 scopus 로고    scopus 로고
    • Dynamic assembly of TRPC1-STIM1-Orai1 ternary complex is involved in store-operated calcium influx. Evidence for similarities in store-operated and calcium release-activated calcium channel components
    • Ong H.L., Cheng K.T., Liu X., et al. Dynamic assembly of TRPC1-STIM1-Orai1 ternary complex is involved in store-operated calcium influx. Evidence for similarities in store-operated and calcium release-activated calcium channel components. J. Biol. Chem. 2007, 282:9105-9116.
    • (2007) J. Biol. Chem. , vol.282 , pp. 9105-9116
    • Ong, H.L.1    Cheng, K.T.2    Liu, X.3
  • 48
    • 45149098247 scopus 로고    scopus 로고
    • Functional requirement for Orai1 in store operated TRPC1-STIM1 channels
    • Cheng K.T., Liu X., Ong H.L., Ambudkar I.S. Functional requirement for Orai1 in store operated TRPC1-STIM1 channels. J. Biol. Chem. 2008, 283:12935-12940.
    • (2008) J. Biol. Chem. , vol.283 , pp. 12935-12940
    • Cheng, K.T.1    Liu, X.2    Ong, H.L.3    Ambudkar, I.S.4
  • 51
    • 57749114666 scopus 로고    scopus 로고
    • 2+ release by mediating the interaction between inositol 1,4,5-trisphosphate receptor and RACK1
    • 2+ release by mediating the interaction between inositol 1,4,5-trisphosphate receptor and RACK1. J. Biol. Chem. 2008, 283:32821-32830.
    • (2008) J. Biol. Chem. , vol.283 , pp. 32821-32830
    • Bandyopadhyay, B.C.1    Ong, H.L.2    Lockwich, T.P.3
  • 53
    • 33745788826 scopus 로고    scopus 로고
    • 2+ signaling dynamics in exocrine cells with total internal reflection microscopy
    • 2+ signaling dynamics in exocrine cells with total internal reflection microscopy. Am. J. Physiol. Gastrointest. Liver Physiol. 2006, 291:146-155.
    • (2006) Am. J. Physiol. Gastrointest. Liver Physiol. , vol.291 , pp. 146-155
    • Won, J.H.1    Yule, D.I.2
  • 54
    • 80052617830 scopus 로고    scopus 로고
    • The dynamic complexity of the TRPC1 channelosome
    • Ong H.L., Ambudkar I.S. The dynamic complexity of the TRPC1 channelosome. Channels (Austin) 2011, 5:424-431.
    • (2011) Channels (Austin) , vol.5 , pp. 424-431
    • Ong, H.L.1    Ambudkar, I.S.2
  • 56
    • 74849118341 scopus 로고    scopus 로고
    • Lipid rafts as a membrane-organizing principle
    • Lingwood D., Simons K. Lipid rafts as a membrane-organizing principle. Science 2010, 327:46-50.
    • (2010) Science , vol.327 , pp. 46-50
    • Lingwood, D.1    Simons, K.2
  • 57
    • 67349169972 scopus 로고    scopus 로고
    • Lipid rafts/caveolae as microdomains of calcium signaling
    • Pani B., Singh B.B. Lipid rafts/caveolae as microdomains of calcium signaling. Cell Calcium 2009, 45:625-633.
    • (2009) Cell Calcium , vol.45 , pp. 625-633
    • Pani, B.1    Singh, B.B.2
  • 58
    • 0034697041 scopus 로고    scopus 로고
    • Assembly of Trp1 in a signaling complex associated with caveolin-scaffolding lipid raft domains
    • Lockwich T.P., Liu X., Singh B.B., et al. Assembly of Trp1 in a signaling complex associated with caveolin-scaffolding lipid raft domains. J. Biol. Chem. 2000, 275:11934-11942.
    • (2000) J. Biol. Chem. , vol.275 , pp. 11934-11942
    • Lockwich, T.P.1    Liu, X.2    Singh, B.B.3
  • 60
    • 79959437055 scopus 로고    scopus 로고
    • STIM proteins and the endoplasmic reticulum-plasma membrane junctions
    • Carrasco S., Meyer T. STIM proteins and the endoplasmic reticulum-plasma membrane junctions. Annu. Rev. Biochem. 2011, 80:973-1000.
    • (2011) Annu. Rev. Biochem. , vol.80 , pp. 973-1000
    • Carrasco, S.1    Meyer, T.2
  • 63
    • 84879383820 scopus 로고    scopus 로고
    • PI(4,5)P(2)-dependent and Ca(2+)-regulated ER-PM interactions mediated by the extended synaptotagmins
    • Giordano F., Saheki Y., Idevall-Hagren O., et al. PI(4,5)P(2)-dependent and Ca(2+)-regulated ER-PM interactions mediated by the extended synaptotagmins. Cell 2013, 153:1494-1509.
    • (2013) Cell , vol.153 , pp. 1494-1509
    • Giordano, F.1    Saheki, Y.2    Idevall-Hagren, O.3
  • 64
    • 84887617011 scopus 로고    scopus 로고
    • 2+ signaling mediated by E-Syt1 and Nir2 at endoplasmic reticulum-plasma membrane junctions
    • 2+ signaling mediated by E-Syt1 and Nir2 at endoplasmic reticulum-plasma membrane junctions. Cell Rep. 2013, 5:813-825.
    • (2013) Cell Rep. , vol.5 , pp. 813-825
    • Chang, C.L.1    Hsieh, T.S.2    Yang, T.T.3
  • 68
    • 73949101745 scopus 로고    scopus 로고
    • Activation of TRPC1 by STIM1 in ER-PM microdomains involves release of the channel from its scaffold caveolin-1
    • Pani B., Ong H.L., Brazer S.C. Activation of TRPC1 by STIM1 in ER-PM microdomains involves release of the channel from its scaffold caveolin-1. Proc. Natl. Acad. Sci. U. S. A. 2009, 106:20087-20092.
    • (2009) Proc. Natl. Acad. Sci. U. S. A. , vol.106 , pp. 20087-20092
    • Pani, B.1    Ong, H.L.2    Brazer, S.C.3
  • 69
    • 84876181767 scopus 로고    scopus 로고
    • Impairment of TRPC1-STIM1 channel assembly and AQP5 translocation compromise agonist-stimulated fluid secretion in mice lacking caveolin1
    • Pani B., Liu X., Bollimuntha S., et al. Impairment of TRPC1-STIM1 channel assembly and AQP5 translocation compromise agonist-stimulated fluid secretion in mice lacking caveolin1. J. Cell Sci. 2013, 126:667-675.
    • (2013) J. Cell Sci. , vol.126 , pp. 667-675
    • Pani, B.1    Liu, X.2    Bollimuntha, S.3


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.