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Autor     Eno Essien Ebong, Sanghee Kim, Natacha DePaola
Titel    Flow regulates intercellular communication in HAEC by assembling functional Cx40 and Cx37 gap junctional channels
Zeitschrift    American Journal of Physiology - Heart and Circulatory Physiology
Ausgabe    290
Jahr    2006
Seiten    H2015–H2023
DOI     :10.1152/ajpheart.00204.2005
URL    http://ajpheart.physiology.org/content/ajpheart/290/5/H2015.full.pdf

Literaturverz.   

ja
Fußnoten    ja
Fragmente    5


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[1.] Haw/Fragment 015 16 - Diskussion
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Ebong et al 2006, Fragment, Gesichtet, Haw, KomplettPlagiat, SMWFragment, Schutzlevel sysop

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Intercellular communication is a key regulator of vascular function[69, 70]. In the vessel wall, cell-to-cell communication occurs by extracellular diffusion and convection of humoral factors or by intercytoplasmic exchange of ions, metabolites, [and small signaling molecules (<1 kDa) via gap junctions.]

69. Haefliger, J.A., P. Nicod, and P. Meda, Contribution of connexins to the function of the vascular wall. Cardiovasc Res, 2004. 62(2): p. 345-56.

70. Ross, R., Cell biology of atherosclerosis. Annu Rev Physiol, 1995. 57: p. 791-804.

INTERCELLULAR COMMUNICATION is a key regulator of vascular function (23, 40). In the vessel wall, cell-to-cell communication occurs by extracellular diffusion and convection of humoral factors or by intercytoplasmic exchange of ions, metabolites, and small signaling molecules (<1 kDa) via gap junctions.

23. Haefliger JA, Nicod P, and Meda P. Contribution of connexins to the function of the vascular wall. Cardiovasc Res 62: 345–356, 2004.

40. Ross R. Cell biology of atherosclerosis. Annu Rev Physiol 57: 791–804, 1995.

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[2.] Haw/Fragment 016 01 - Diskussion
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Endothelial gap junctions are channels that permit and strictly regulate communication throughout the endothelial monolayer and between endothelial cells and adjacent smooth muscle and circulating blood cells. Endothelial cell migration and growth, particularly following injury and during angiogenesis, depend on communication through gap junctions[71-75]. In addition, gap junctions coordinate vascular tone and vasomotion [76-78] and participate in the regulation of immunoinflammatory responses[79, 80].

[...] Gap junctions are formed by a pair of hemichannels called connexons, each contributed by one of two neighboring cells. Connexons are composed of six connexin monomer subunits arranged around a central pore(Fig.1.6.)[82].


71. Kwak, B.R., et al., Inhibition of endothelial wound repair by dominant negative connexin inhibitors. Mol Biol Cell, 2001. 12(4): p. 831-45.

72. Larson, D.M., et al., Differential regulation of connexin43 and connexin37 in endothelial cells by cell density, growth, and TGF-beta1. Am J Physiol, 1997. 272(2 Pt 1): p. C405-15.

73. Pepper, M.S., et al., Junctional communication is induced in migrating capillary endothelial cells. J Cell Biol, 1989. 109(6 Pt 1): p. 3027-38.

74. Xie, H.Q. and V.W. Hu, Modulation of gap junctions in senescent endothelial cells. Exp Cell Res, 1994. 214(1): p. 172-6.

75. Yeh, H.I., et al., Age-related alteration of gap junction distribution and connexin expression in rat aortic endothelium. J Histochem Cytochem, 2000. 48(10): p. 1377-89.

76. Chaytor, A.T., W.H. Evans, and T.M. Griffith, Central role of heterocellular gap junctional communication in endothelium-dependent relaxations of rabbit arteries. J Physiol, 1998. 508 ( Pt 2): p. 561-73.

77. Christ, G.J., et al., Gap junctions in vascular tissues. Evaluating the role of intercellular communication in the modulation of vasomotor tone. Circ Res, 1996. 79(4): p. 631-46.

78. de Wit, C., et al., Impaired conduction of vasodilation along arterioles in connexin40-deficient mice. Circ Res, 2000. 86(6): p. 649-55.

79. Oviedo-Orta, E., R.J. Errington, and W.H. Evans, Gap junction intercellular communication during lymphocyte transendothelial migration. Cell Biol Int, 2002. 26(3): p. 253-63.

80. Wong, C.W., T. Christen, and B.R. Kwak, Connexins in leukocytes: shuttling messages? Cardiovasc Res, 2004. 62(2): p. 357-67.

82. Sohl, G. and K. Willecke, Gap junctions and the connexin protein family. Cardiovasc Res, 2004. 62(2): p. 228-32.

Endothelial gap junctions are channels that permit and strictly regulate communication throughout the endothelial monolayer and between endothelial cells and adjacent smooth muscle and circulating blood cells. Endothelial cell migration and growth, particularly following injury and during angiogenesis, depend on communication through gap junctions (31, 33, 38, 51, 52). In addition, gap junctions coordinate vascular tone and vasomotion (11, 13, 17) and participate in the regulation of immunoinflammatory responses (36, 50).

Gap junctions are formed by a pair of hemichannels called connexons, each contributed by one of two neighboring cells. Connexons are composed of six connexin monomer subunits arranged around a central pore.


11. Chaytor AT, Evans WH, and Griffith TM. Central role of heterocellular gap junctional communication in endothelium-dependent relaxations of rabbit arteries. J Physiol 508: 561–573, 1998.

13. Christ GJ, Spray DC, el-Sabban M, Moore LK, and Brink PR. Gap junctions in vascular tissues. Evaluating the role of intercellular communication in the modulation of vasomotor tone. Circ Res 79: 631–646, 1996.

17. De Wit C, Roos F, Bolz SS, Kirchhoff S, Krüger O, Willecke K, and Pohl U. Impaired conduction of vasodilation along arterioles in connexin40-deficient mice. Circ Res 86: 649–655, 2000.

31. Kwak BR, Pepper MS, Gros DB, and Meda P. Inhibition of endothelial wound repair by dominant negative connexin inhibitors. Mol Biol Cell 12: 831–845, 2001.

33. Larson DM, Wrobleski MJ, Sagar GD, Westphale EM, and Beyer EC. Differential regulation of connexin43 and connexin37 in endothelial cells by cell density, growth, and TGF-beta1. Am J Physiol Cell Physiol 272: C405–C415, 1997.

36. Oviedo-Orta E, Errington RJ, and Evans WH. Gap junction intercellular communication during lymphocyte transendothelial migration. Cell Biol Int 26: 253–263, 2002.

38. Pepper MS, Spray DC, Chanson M, Montesano R, Orci L, and Meda P. Junctional communication is induced in migrating capillary endothelial cells. J Cell Biol 109: 3027–3038, 1989.

50. Wong CW, Christen T, and Kwak BR. Connexins in leukocytes: shuttling messages? Cardiovasc Res 62: 357–367, 2004.

51. Xie HQ and Hu VW. Modulation of gap junctions in senescent endothelial cells. Exp Cell Res 214: 172–176, 1994.

52. Yeh HI, Chang HM, Lu WW, Lee YN, Ko YS, Severs NJ, and Tsai CH. Age-related alteration of gap junction distribution and connexin expression in rat aortic endothelium. J Histochem Cytochem 48: 1377–1389, 2000.

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[3.] Haw/Fragment 017 10 - Diskussion
Zuletzt bearbeitet: 2014-10-12 16:54:35 Schumann
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Connexins 37, 40, and 43 (Cx37, Cx40, Cx43, respectively) are the major gap junction proteins expressed in vascular endothelial cells[85-89]. These proteins are very dynamic, exhibiting rapid turnover times and variable expression patterns. Because of the unique gating and permselective characteristics of Cx37, Cx40, and Cx43, different combinations of these connexin isoforms contribute to homo- or heteromeric connexons and homo- or heterotypic gap junctions leading to a variety of channel types with different functional properties[83, 90-96].

83. Kumar, N.M. and N.B. Gilula, The gap junction communication channel. Cell, 1996. 84(3): p. 381-8.

85. Bruzzone, R., et al., Connexin40, a component of gap junctions in vascular endothelium, is restricted in its ability to interact with other connexins. Mol Biol Cell, 1993. 4(1): p. 7-20.

86. Larson, D.M., C.C. Haudenschild, and E.C. Beyer, Gap junction messenger RNA expression by vascular wall cells. Circ Res, 1990. 66(4): p. 1074-80.

87. Little, T.L., E.C. Beyer, and B.R. Duling, Connexin 43 and connexin 40 gap junctional proteins are present in arteriolar smooth muscle and endothelium in vivo. Am J Physiol, 1995. 268(2 Pt 2): p. H729-39.

88. Reed, K.E., et al., Molecular cloning and functional expression of human connexin37, an endothelial cell gap junction protein. J Clin Invest, 1993. 91(3): p. 997-1004.

89. Van Rijen, H., et al., Gap junctions in human umbilical cord endothelial cells contain multiple connexins. Am J Physiol, 1997. 272(1 Pt 1): p. C117-30.

90. Beblo, D.A. and R.D. Veenstra, Monovalent cation permeation through the connexin40 gap junction channel. Cs, Rb, K, Na, Li, TEA, TMA, TBA, and effects of anions Br, Cl, F, acetate, aspartate, glutamate, and NO3. J Gen Physiol, 1997. 109(4): p. 509-22.

91. Bruzzone, R., T.W. White, and D.A. Goodenough, The cellular Internet: on-line with connexins. Bioessays, 1996. 18(9): p. 709-18.

92. Bruzzone, R., T.W. White, and D.L. Paul, Connections with connexins: the molecular basis of direct intercellular signaling. Eur J Biochem, 1996. 238(1): p. 1-27.

93. Elfgang, C., et al., Specific permeability and selective formation of gap junction channels in connexin-transfected HeLa cells. J Cell Biol, 1995. 129(3): p. 805-17.

94. Veenstra, R.D., Size and selectivity of gap junction channels formed from different connexins. J Bioenerg Biomembr, 1996. 28(4): p. 327-37.

95. Wang, H.Z. and R.D. Veenstra, Monovalent ion selectivity sequences of the rat connexin43 gap junction channel. J Gen Physiol, 1997. 109(4): p. 491-507.

96. White, T.W. and R. Bruzzone, Multiple connexin proteins in single intercellular channels: connexin compatibility and functional consequences. J Bioenerg Biomembr, 1996. 28(4): p. 339-50.

Connexin 37, 40, and 43 (Cx37, Cx40, Cx43, respectively) are the major gap junction proteins expressed in vascular endothelial cells (7, 32, 34, 39, 45). These proteins are very dynamic, exhibiting rapid turnover times and variable expression patterns. Because of the unique gating and permselective characteristics of Cx37, Cx40, and Cx43, different combinations of these connexin isoforms contribute to homo- or heteromeric connexons and homo- or heterotypic gap junctions leading to a variety of channel types with different functional properties (1, 8, 9, 19, 28, 47–49).

1. Beblo DA and Veenstra RD. Monovalent cation permeation through the connexin40 gap junction channel: Cs, Rb, K, Na, Li, TEA, TMA, TBA, and effects of anions Br, Cl, F, acetate, aspartate, glutamate, and NO3. J Gen Physiol 109: 509–522, 1997.

7. Bruzzone R, Haefliger JA, Gimlich RL, and Paul DL. Connexin40, a component of gap junctions in vascular endothelium, is restricted in its ability to interact with other connexins. Mol Biol Cell 4: 7–20, 1993.

8. Bruzzone R, White TW, and Goodenough DA. The cellular internet: on-line with connexins. Bioessays 18: 709–718, 1996.

9. Bruzzone R, White TW, and Paul DL. Connections with connexins: the molecular basis of direct intercellular signaling. Eur J Biochem 238: 1–27, 1996.

19. Elfgang C, Eckert R, Lichtenberg-Frate´ H, Butterweck A, Traub O, Klein TA, Hüsler DF, and Willecke K. Specific permeability and selective formation of gap junction channels in connexin-transfected HeLa cells. J Cell Biol 129: 805–817, 1995.

28. Kumar NM and Gilula NB. The gap junction communication channel. Cell 84: 381–388, 1996.

29. Kwak BR and Jongsma HJ. Selective inhibition of gap junction channel activity by synthetic peptides. J Physiol 516: 679–685, 1999.

32. Larson DM, Haudenschild CC, and Beyer EC. Gap junction messenger RNA expression by vascular wall cells. Circ Res 66: 1074–1080, 1990.

34. Little TL, Beyer EC, and Duling BR. Connexin 43 and connexin 40 gap junctional proteins are present in arteriolar smooth muscle and endothelium in vivo. Am J Physiol Heart Circ Physiol 268: H729–H739, 1995.

39. Reed KE, Westphale EM, Larson DM, Wang HZ, Veenstra RD, and Beyer EC. Molecular cloning and functional expression of human connexin37, an endothelial cell gap junction protein. J Clin Invest 91: 997–1004, 1993.

45. Van Rijen H, van Kempen MJ, Analbers LJ, Rook MB, van Ginneken AC, Gros D, and Jongsma HJ. Gap junctions in human umbilical cord endothelial cells contain multiple connexins. Am J Physiol Cell Physiol 272: C117–C130, 1997.

47. Veenstra RD. Size and selectivity of gap junction channels formed from different connexins. J Bioenerg Biomembr 28:b 327–337, 1996.

48. Wang HZ and Veenstra RD. Monovalent ion selectivity sequences of the rat connexin43 gap junction channel. J Gen Physiol 109: 491–507, 1997.

49. White TW and Bruzzone R. Multiple connexin proteins in single intercellular channels: connexin compatibility and functional consequences. J Bioenerg Biomembr 28: 339–350, 1996.

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[4.] Haw/Fragment 019 01 - Diskussion
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[Although the extent of combinations of different connexins within connexons and] channels remains unclear, immunohistochemical and immunocytochemical studies demonstrate differential expression and localization patterns of all three vascular connexins in the endothelium, depending on species[97], vascular bed[98-100], and local hemodynamics[101]. In vivo studies implicate Cx40 as the constitutive vascular gap junction protein across species and vascular bed, playing an important role in coupling between cells in the vascular wall[97].

97. van Kempen, M.J. and H.J. Jongsma, Distribution of connexin37, connexin40 and connexin43 in the aorta and coronary artery of several mammals. Histochem Cell Biol, 1999. 112(6): p. 479-86.

98. Hill, C.E., et al., Heterogeneity in the distribution of vascular gap junctions and connexins: implications for function. Clin Exp Pharmacol Physiol, 2002. 29(7): p. 620-5.

99. Pepper, M.S., et al., Coupling and connexin 43 expression in microvascular and large vessel endothelial cells. Am J Physiol, 1992. 262(5 Pt 1): p. C1246-57.

100. Yeh, H.I., et al., Individual gap junction plaques contain multiple connexins in arterial endothelium. Circ Res, 1998. 83(12): p. 1248-63.

101. Gabriels, J.E. and D.L. Paul, Connexin43 is highly localized to sites of disturbed flow in rat aortic endothelium but connexin37 and connexin40 are more uniformly distributed. Circ Res, 1998. 83(6): p. 636-43.

Although the extent of combinations of different connexins within connexons and channels remains unclear, immunohistochemical and immunocytochemical studies demonstrate differential expression and localization patterns of all three vascular connexins in endothelium, depending on species (44), vascular bed (25, 37, 53), and local hemodynamics (21). In vivo studies implicate Cx40 as the constitutive vascular gap junction protein across species and vascular bed, playing an important role in coupling between cells in the vascular wall (44).

21. Gabriels JE and Paul DL. Connexin43 is highly localized to sites of disturbed flow in rat aortic endothelium but connexin37 and connexin40 are more uniformly distributed. Circ Res 83: 636–643, 1998.

25. Hill CE, Rummery N, Hickey H, and Sandow SL. Heterogeneity in the distribution of vascular gap junctions and connexins: implications for function. Clin Exp Pharmacol Physiol 29: 620–625, 2002.

37. Pepper MS, Montesano R, el Aoumari A, Gros D, Orci L, and Meda P. Coupling and connexin 43 expression in microvascular and large vessel endothelial cells. Am J Physiol Cell Physiol 262: C1246–C1257, 1992.

44. Van Kempen MJ and Jongsma HJ. Distribution of connexin37, connexin40 and connexin43 in the aorta and coronary artery of several mammals. Histochem Cell Biol 112: 479–486, 1999.

53. Yeh HI, Rothery S, Dupont E, Coppen SR, and Severs NJ. Individual gap junction plaques contain multiple connexins in arterial endothelium. Circ Res 83: 1248–1263, 1998.

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[5.] Haw/Fragment 023 19 - Diskussion
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Connexin 37 and Connexin 40 (Cx37, Cx40) are the major gap junction proteins expressed in vascular endothelial cells[85-89]. These proteins are very dynamic, exhibiting rapid turnover times and variable expression patterns. Although the extent of combinations of different connexins within connexons and channels remains unclear, immunohistochemical and immunocytochemical studies demonstrate differential expression and localization patterns of both vascular connexins in endothelium, depending on species[97], vascular bed[98-100], and local hemodynamics[101].[...] For the microcirculation in vivo studies implicate Cx40 as the constitutive vascular gap junction protein across species [and vascular bed, playing an important role in coupling between cells in the vascular wall[78, 97-98], particularly in response to changes in tissue metabolic demand.]

78. de Wit, C., et al., Impaired conduction of vasodilation along arterioles in connexin40-deficient mice. Circ Res, 2000. 86(6): p. 649-55.

85. Bruzzone, R., et al., Connexin40, a component of gap junctions in vascular endothelium, is restricted in its ability to interact with other connexins. Mol Biol Cell, 1993. 4(1): p. 7-20.

86. Larson, D.M., C.C. Haudenschild, and E.C. Beyer, Gap junction messenger RNA expression by vascular wall cells. Circ Res, 1990. 66(4): p. 1074-80.

87. Little, T.L., E.C. Beyer, and B.R. Duling, Connexin 43 and connexin 40 gap junctional proteins are present in arteriolar smooth muscle and endothelium in vivo. Am J Physiol, 1995. 268(2 Pt 2): p. H729-39.

88. Reed, K.E., et al., Molecular cloning and functional expression of human connexin37, an endothelial cell gap junction protein. J Clin Invest, 1993. 91(3): p. 997-1004.

89. Van Rijen, H., et al., Gap junctions in human umbilical cord endothelial cells contain multiple connexins. Am J Physiol, 1997. 272(1 Pt 1): p. C117-30.

97. van Kempen, M.J. and H.J. Jongsma, Distribution of connexin37, connexin40 and connexin43 in the aorta and coronary artery of several mammals. Histochem Cell Biol, 1999. 112(6): p. 479-86. 98. Hill, C.E., et al., Heterogeneity in the distribution of vascular gap junctions and connexins: implications for function. Clin Exp Pharmacol Physiol, 2002. 29(7): p. 620-5.

99. Pepper, M.S., et al., Coupling and connexin 43 expression in microvascular and large vessel endothelial cells. Am J Physiol, 1992. 262(5 Pt 1): p. C1246-57.

100. Yeh, H.I., et al., Individual gap junction plaques contain multiple connexins in arterial endothelium. Circ Res, 1998. 83(12): p. 1248-63.

101. Gabriels, J.E. and D.L. Paul, Connexin43 is highly localized to sites of disturbed flow in rat aortic endothelium but connexin37 and connexin40 are more uniformly distributed. Circ Res, 1998. 83(6): p. 636-43.

Connexin 37, 40, and 43 (Cx37, Cx40, Cx43, respectively) are the major gap junction proteins expressed in vascular endothelial cells (7, 32, 34, 39, 45). These proteins are very dynamic, exhibiting rapid turnover times and variable expression patterns. [...]

Although the extent of combinations of different connexins within connexons and channels remains unclear, immunohistochemical and immunocytochemical studies demonstrate differential expression and localization patterns of all three vascular connexins in endothelium, depending on species (44), vascular bed (25, 37, 53), and local hemodynamics (21). In vivo studies implicate Cx40 as the constitutive vascular gap junction protein across species and vascular bed, playing an important role in coupling between cells in the vascular wall (44).


7. Bruzzone R, Haefliger JA, Gimlich RL, and Paul DL. Connexin40, a component of gap junctions in vascular endothelium, is restricted in its ability to interact with other connexins. Mol Biol Cell 4: 7–20, 1993.

21. Gabriels JE and Paul DL. Connexin43 is highly localized to sites of disturbed flow in rat aortic endothelium but connexin37 and connexin40 are more uniformly distributed. Circ Res 83: 636–643, 1998.

25. Hill CE, Rummery N, Hickey H, and Sandow SL. Heterogeneity in the distribution of vascular gap junctions and connexins: implications for function. Clin Exp Pharmacol Physiol 29: 620–625, 2002.

32. Larson DM, Haudenschild CC, and Beyer EC. Gap junction messenger RNA expression by vascular wall cells. Circ Res 66: 1074–1080, 1990.

34. Little TL, Beyer EC, and Duling BR. Connexin 43 and connexin 40 gap junctional proteins are present in arteriolar smooth muscle and endothelium in vivo. Am J Physiol Heart Circ Physiol 268: H729–H739, 1995.

37. Pepper MS, Montesano R, el Aoumari A, Gros D, Orci L, and Meda P. Coupling and connexin 43 expression in microvascular and large vessel endothelial cells. Am J Physiol Cell Physiol 262: C1246–C1257, 1992.

39. Reed KE, Westphale EM, Larson DM, Wang HZ, Veenstra RD, and Beyer EC. Molecular cloning and functional expression of human connexin37, an endothelial cell gap junction protein. J Clin Invest 91: 997–1004, 1993.

44. Van Kempen MJ and Jongsma HJ. Distribution of connexin37, connexin40 and connexin43 in the aorta and coronary artery of several mammals. Histochem Cell Biol 112: 479–486, 1999.

45. Van Rijen H, van Kempen MJ, Analbers LJ, Rook MB, van Ginneken AC, Gros D, and Jongsma HJ. Gap junctions in human umbilical cord endothelial cells contain multiple connexins. Am J Physiol Cell Physiol 272: C117–C130, 1997.

53. Yeh HI, Rothery S, Dupont E, Coppen SR, and Severs NJ. Individual gap junction plaques contain multiple connexins in arterial endothelium. Circ Res 83: 1248–1263, 1998.

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Der Text wird zum zweiten mal verwendet, siehe Fragment 017 10 und Fragment 019 01.

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