Skip to main content
SpringerLink
Log in

Microtubules in cardiac toxicity and disease

  • Published:
Cardiovascular Toxicology Aims and scope Submit manuscript

An Erratum to this article was published on 01 September 2002

Abstract

Microtubules (MTs) are dynamic, cytoskeletal fibers that are found in every eukaryotic cell type. MTs serve a wide range of functions, including cell division, membrane and vesicle transport, and motility. As such, MTs play pivotal roles in cardiac development and function. Agents that disrupt normal MT function, including such therapeutic agents as vincristine and paclitaxel, have also been shown to affect essential cardiac activities such as sarcomere mechanics, beat rate, and the secretion of important molecules (e.g., atrial natriuretic factor). Disease states that lead to either ischemia- or pressureoverload-induced cardiac hypertrophy also alter the microtubule cytoskeleton in several ways. A fuller understanding of the contributions of MTs to cardiac development and function will be necessary to minimize the deleterious, side effects of the therapeutic application of MT-disrupting drugs. This review summarizes current hypotheses and experimental results that demonstrate the central role of MTs in heart cell function and disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hiller, G. and Weber, K. (1978). Radioimmunoassay, for tubulin: a quantitative comparison of the tubulin content of different established tissue culture cells and tissues. Cell 14:795–804.

    PubMed  CAS  Google Scholar 

  2. Klein, I. (1983). Colchicine stimulates the rate of contraction of heart cells in culture. Card. Res. 17:459–465.

    CAS  Google Scholar 

  3. Webster, D.R. (1997). Regulation of posttranslationally modified microtubule populations during neonatal cardiac development. J. Mol. Cell. Cardiol. 29:1747–1761.

    PubMed  CAS  Google Scholar 

  4. Ishibashi, Y., Tsutsui, H., Yamamoto, S., Takahashi, M., Imanaka-Yoshida, K., Yoshida, T. et al. (1996). Role of microtubules in myocyte contractile dysfunction during cardiac hypertrophy in the rat. Am. J. Physiol. Heart Circ. Physiol. 271:H1978-H1987.

    CAS  Google Scholar 

  5. Samuel, J.-L., Schwartz, K., Lompre, A.-M., Delcayre, C., Marotte, F., Swynghedauw, B., et al. (1983). Immunological quantitation and localization of tubulin in adult rat heart isolated myocytes. Eur. J. Cell Biol. 31:99–106.

    PubMed  CAS  Google Scholar 

  6. Hoyle, H.D., and Raff, E.C. (1990). Two Drosophila beta tubulin isoforms are not functionally equivalent. J. Cell Biol. 111:1009–1026.

    PubMed  CAS  Google Scholar 

  7. Narishige, T., Blade, K.L., Ishibashi, Y., Nagai, T., Hamawaki, M., Menick, D.R., et al. (1999). Cardiac hypertrophic and developmental regulation of the β-tubulin multigene family. J. Biol. Chem. 274:9692–9697.

    PubMed  CAS  Google Scholar 

  8. Nogales E. (2000). Structural insights into microtubule function. Annu. Rev. Biochem. 69:277–302.

    PubMed  CAS  Google Scholar 

  9. Wang, N., Yan, K., and Rasenick, M.M. (1990). Tubulin binds specifically to the signal-transducing proteins, Gs alpha and Gi alpha 1. J. Biol. Chem. 265:1239–1242.

    PubMed  CAS  Google Scholar 

  10. Mitchison, T. and Kirschner, M. (1984) Dynamic instability of microtubule growth. Nature 312:237–242.

    PubMed  CAS  Google Scholar 

  11. Kirschner, M. and Mitchison, T. (1986). Beyond self-assembly: from microtubules to morphogenesis. Cell 45:329–342.

    PubMed  CAS  Google Scholar 

  12. Wilson, L. and Jordan, M.J. (1994). Microtubules, in Pharmacological Probes of Microtubule Function. (Hyams, J.S and Lloyd, C.W., eds.), Wiley-Liss, New York.

    Google Scholar 

  13. Ke, Y., Ye, K., Grossniklaus, H.E., Archer, D.R., Joshi, H.C., and Kapp, J.A. (2000). Noscapine inhibits tumor growth with little toxicity to normal tissues or inhibition of immune responses. Cancer Immunol. Immunother. 49: 217–225.

    PubMed  CAS  Google Scholar 

  14. Rowinsky, E.K. and Donehower, R.C. (1995). Paclitaxel (taxol). N. Engl. J. Med. 332:1004–1014.

    PubMed  CAS  Google Scholar 

  15. Nguyen, H.L., Gruber, D., and Bulinski, J.C. (1999) Microtubule-associated protein 4 (MAP4) regulates assembly, protomer-polymer partitioning and synthesis of tubulin in cultured cells. J. Cell Sci. 1112:1813–1824.

    Google Scholar 

  16. Hirokawa, N. (1998). Kinesin and dynein superfamily proteins and the mechanism of organelle transport. Science 279:519–526.

    PubMed  CAS  Google Scholar 

  17. Aizawa, H., Emori, Y., Murofushi, H., Kawasaki, H., Sakai, H., and Suzuki, K. (1990). Molecular cloning of a ubiquitously distributed microtubule-associated protein with Mr 190, 000. J. Biol. Chem. 265:13,849–13,855.

    CAS  Google Scholar 

  18. Chapin, S.J., Lue, C.-M., Yu, M.T., and Bulinski, J.C. (1995). Differential expression of alternatively spliced forms of MAP4: a repertoire of structurally different microtubule-binding domains. Biochemistry 34:2289–2301.

    PubMed  CAS  Google Scholar 

  19. Mangan, M.E. and Olmsted, J.B. (1996). A muscle-specific variant of microtubule-associated protein 4 (MAP4) is required in myogenesis Development 122:771–781.

    PubMed  CAS  Google Scholar 

  20. Stassen, M.P., Thole, H.H. Schaaf, C., Marquart, A.U., Sinner, K., and Gehrig, H. (1996). Chicken microtubule-associated protein 4 (MAP4): a novel member of the MAP4 family. Histochem. Cell Biol. 106:341–349.

    PubMed  CAS  Google Scholar 

  21. Sato, H., Nagai, T., Kuppuswamy, D., Narishige, T., Koide, M., Menick, D.R., et al. (1997). Microtubule stabilization in pressure overload cardiac hypertrophy. J. Cell Biol. 139: 963–973.

    PubMed  CAS  Google Scholar 

  22. Lai, F., Fernald, A.A., Zhao, N., and Le Beau, M.M. (2000). cDNA cloning, expression pattern, genomic, structure and chromosomal location of RAB6KIFL, a human kinesin-like gene. Gene 248:117–125.

    PubMed  CAS  Google Scholar 

  23. Muresan, V., Abramson, T., Lyass, A., Winter, D., Porro, E., Hong, F., et al. (1998). KIF3C and KIF3A form a novel neuronal heteromeric, kinesin that associates with membrane vesciles. Mol. Biol. Cell 9:637–652.

    PubMed  CAS  Google Scholar 

  24. Nakagawa, T., Tanaka, Y., Matsuoka E., Kondo, S., Okada, Y., Noda, Y., et al. (1997). Identification and classification of 16 new kinesin superfamily (KIF) proteins in mouse genome. Proc. Natl. Acad. Sci. USA 94:9654–9659.

    PubMed  CAS  Google Scholar 

  25. Yoshida, T., Takanari, H., and Izutsu, K. (1992). Distribution of cytoplasmic and axonemal dyneins in rat tissues. J. Cell Sci. 101:579–587.

    PubMed  CAS  Google Scholar 

  26. Macrae, T.H. (1997). Tubulin posttranslational modifications. Enzymes and the mechanisms of action. Eur. J. Biochem. 244:265–278.

    PubMed  CAS  Google Scholar 

  27. Idriss, H.T. (2000). Man to trypanosome: the tubulin tyrosination/detyrosination cyclerevisited. Cell Motil. Cytoskel. 45:173–184.

    CAS  Google Scholar 

  28. Kreitzer, G., Liao, G., and Gundersen, G.G. (1999). Detyrosination of tubulin regulates the interaction of intermediate filaments with microtubules in vivo via a kinesin-dependent mechanism. Mol. Biol. Cell 10:1105–1118.

    PubMed  CAS  Google Scholar 

  29. Webster, D.R. (1997). Neonatal rat cardiomyocytes possess a large population of stable microtubules that is enriched in post-translationally modified subunits. J. Mol. Cell. Cardiol. 29:2813–2824.

    PubMed  CAS  Google Scholar 

  30. Oakley, B.R. (1994). Microtubules, in γ-Tubulin. (Hyams, J.S., and Lloyd, C.W., eds.), Wiley-Liss, New York.

    Google Scholar 

  31. Cassimeris, L., Pryer, N.K., and Salmon, E.D. (1988). Real-time observations of microtubule dynamic instability in living cells. J. Cell Biol. 107:2223–2232.

    PubMed  CAS  Google Scholar 

  32. Webster, D.R., Gundersen, G.G., Bulinski, J.C., and Borisy, G.G. (1987) Assembly and turnover of detyrosinated tubulin in vivo. J. Cell. Biol. 105:265–276.

    PubMed  CAS  Google Scholar 

  33. Baas, P.W. and Black, M.M. (1990). Individual microtubules in the axon consist of domains that differ in both composition and stability. J. Cell Biol. 111:495–509.b

    PubMed  CAS  Google Scholar 

  34. Bulinski, J.C., Richards, J.E., and Piperno, G. (1988). Posttranslational modifications of α-tubulin: detyrosination and acetylation differentiate populations of interphase microtubules in cultured cells. J. Cell Biol. 106:1213–1220.

    PubMed  CAS  Google Scholar 

  35. Kreis, T. (1987). Microtubules containing detyrosinated tubulin are less dynamic. EMBO J. 6:2597–2606.

    PubMed  CAS  Google Scholar 

  36. Schulze, E., Asai, D.J., Bulinski, J.C., and Kirschner, M. (1987). Posttranslational modifications and microtubule stability. J. Cell Biol. 105:2167–2177.

    PubMed  CAS  Google Scholar 

  37. Webster, D.R., Gundersen, G.G., Bulinski, J.C., and Borisy, G.G. (1987). Differential turnover of tyrosinated, and detyrosinated microtubules. Proc. Natl. Acad. Sci. USA 84: 9040–9044.

    PubMed  CAS  Google Scholar 

  38. Kronebusch, P.J., and Singer, S.J. (1987). The microtubule-organizing complex and the Golgi apparatus are colocalized around the entire nuclear envelope of interphase cardiac myocytes. J. Cell Sci. 88:25–34.

    PubMed  Google Scholar 

  39. Goldstein, M.A. and Entman, M.L. (1979). Microtubules in mammalian heart muscle. J. Cell Biol. 80:183–195.

    PubMed  CAS  Google Scholar 

  40. Saetersdal, T., Greve, G., and Dalen, H. (1990). Associations between beta-tubulin and mitochondria in adult isolated heart myocytes as shown by immunofluorescence and immunoelectron microscopy. Histochemistry 95:1–10.

    PubMed  CAS  Google Scholar 

  41. Rappaport, L., Samuel, J.L., Bertier-Savalle, B., Marotte, F., and Schwartz, K. (1985). Microtubules and desmin filaments during the onset of heart growth in the rat. Basic Res. Cardiol. 80:129–132.

    PubMed  Google Scholar 

  42. Samuel, J.L., Bertier, B., Bugaisky, L., Marotte, F., Swynghedauw, B., Schwartz, K., et al. (1984) Different distributions of microtubules, desmin filaments and isomyosins during the onset of cardiac hypertrophy in the rat. Eur. J. Cell Biol. 34:300–306.

    PubMed  CAS  Google Scholar 

  43. Tsutsui, H., Ishihara, K. and Cooper, G., IV. (1993). Cytoskeletal role in the contractile, dysfunction of hypertrophied myocardium. Science 260:682–687.

    PubMed  CAS  Google Scholar 

  44. Iida, H. and Shibata, Y. (1991). Functional Golgi units in microtubule-disrupted cultured atrial myocytes. J. Histochem. Cytochem. 39: 1349–1355.

    PubMed  CAS  Google Scholar 

  45. Perhonen, M., Sharp, W.W., and Russell, B. (1998). Microtubules are needed for dispersal of a-myosin heavy chain mRNA in rat neonatal cardiac myocytes. J. Mol. Cell. Cardiol. 30:1713–1722.

    PubMed  CAS  Google Scholar 

  46. Severson, D.L. and Carroll, R. (1989). Effect of taxol on the heparin-induced secretion of lipoprotein lipase from cardiac myocytes. Mol. Cell. Biochem. 88:17–22.

    PubMed  CAS  Google Scholar 

  47. Saetersdal, T., Larsen, T.H., and Roli, J. (1995). Expression of fibronectin, laminin and ribosomes in normal and nocodazole-treated neonatal heart cells in culture: a study by laser scanning confocal microscopy and immunocytochemistry. Cell Tissue Res. 28:11–22.

    Google Scholar 

  48. Larsen, T.H., Huitfeldt, H.S., Myking, O., and Saetersdal, T. (1993). Microtubule-associated distribution of specific granules and secretion of atrial natriuretic factor in primary cultures of rat cardiomyocytes. Cell Tissue Res. 272: 201–210.

    PubMed  CAS  Google Scholar 

  49. Yonemochi, H., Yasunaga, S., Teshima, Y., Takahashi, N., Nakagawa, M., Ito, M., et al. (2000). Rapid electrical stimulation of contraction reduces the density of ββ-adrenergic receptors and responsiveness of cultured neonatal rat cardiomyocytes. Circulation 101:2625–2630.

    PubMed  CAS  Google Scholar 

  50. Limas, C.J. and Limas, C. (1983). Involvement of microtubules in the isoproterenol-induced “down”-regulation of myocardial β-adrenergic receptors. Biochim. Biophys. Acta 735:181–184.

    PubMed  CAS  Google Scholar 

  51. Hori, M., Sato, H., Iwai, K., Sato, H., Inoue, M., Kitabatake, A., et al. (1992). Norepinephrine disrupts cytoskeletal framework of microtubules in rat hearts. Jpn. Circ. J. 56:462–468.

    PubMed  CAS  Google Scholar 

  52. Gregorio, C.C., and Antin, P.B. (2000). To the heart of myofibril assenmbly. TICB 10:355–362.

    CAS  Google Scholar 

  53. Warren, R.H. (1974) Microtubular organization in elongating myogenic cells. J. Cell Biol. 63:550–566.

    PubMed  CAS  Google Scholar 

  54. Bischoff, R. and Holtzer, H. (1968). The effect of mitotic inhibitors on myogenesis in vitro. J. Cell Biol. 36:111–127.

    Google Scholar 

  55. Fransen, M.E. and Lernanski L.F. (1989). Studies of heart development in normal and cardiac lethal mutant axolotls: a review. Scanning Microsc. 3:1101–1115, discussion 1115–1106.

    PubMed  CAS  Google Scholar 

  56. Dabiri, G.A., Turnacioglu, K.K., Sanger, J.M., and Sanger, J.W. (1997). Myofibrillogenesis visualized in living embryonic cardiomyocytes. Proc. Natl. Acad. Sci. USA 94:9493–9498.

    PubMed  CAS  Google Scholar 

  57. Atherton, B.T., Meyer, D.M., and Simpson, D.G. (1986). Assembly and remodelling of myofibrils and intercalated discs in cultured neonatal rat heart cells. J. Cell Sci. 86: 233–248.

    PubMed  CAS  Google Scholar 

  58. Antin, P.B., Forry-Schaudies, S., Friedman, T.M., Tapscott, S.J., and Holtzer, H. (1981). Taxol induces postmitotic myoblasts to assemble interdigitating microtubule-myosin arrays that exclude actin filaments. J. Cell Biol. 90:300–308.

    PubMed  CAS  Google Scholar 

  59. Toyama, Y., Forry-Schaudies, S., Hoffman, B., and Holtzer, H. (1982). Effects of taxol and Colcemid on myofibrillogenesis. Proc. Natl. Acad. Sci. USA 79:6556–6560.

    PubMed  CAS  Google Scholar 

  60. Shimo-Oka, T., Hayashi, M., and Watanabe, Y. (1980). Tubulin-myosin interaction. Some properties of binding between tubulin and myosin. Biochemistry 19:4921–4926.

    PubMed  CAS  Google Scholar 

  61. Schweiger, S., Foerster, J., Lehmann, T., Suckow, V., Muller, Y.A., Walter, G., et al. (1999). The Opitz syndrome gene product, MID1, associates with microtubules. Proc. Natl. Acad. Sci. USA 96:2794–2799.

    PubMed  CAS  Google Scholar 

  62. Centner, T., Yano, J., Kimura, E., McElhinny, A.S., Pelin, K., Witt, C.C., et al. (2001) Identification of muscle specific ring finger proteins as potential regulators of the titin kinase domain. J. Mol. Biol. 306:717–726.

    PubMed  CAS  Google Scholar 

  63. Griparic, L. and Keller, T.C.S.I. (1998). Identification and expression of two novel CLIP-170/restin isoforms expressed predominantly in muscle. Biochim. Biophys. Acta 1405: 35–46.

    PubMed  CAS  Google Scholar 

  64. Lampidis, T.J., Trevorrow, K.W., and Rubin, R.W. (1986). Effects of colchicine on cardiac cell function indicate possible role for membrane surface tubulin. Exp. Cell Res. 164:463–470.

    PubMed  CAS  Google Scholar 

  65. Lampidis, T.J., Kolonias, D., Savaraj, N., and Rubin, R.W. (1992). Cardiostimulatory and antiarrhythmic activity of tubulin-binding agents. Proc. Natl. Acad. Sci. USA 89: 1256–1260.

    PubMed  CAS  Google Scholar 

  66. Webster, D.R. and Patrick, D.L. (2000). Beating rate of isolated neonatal cardiomyocytes is regulated by the stable microtubule subset. Am. J. Physiol. Heart Circ. Physiol. 47:H1653-H1661.

    Google Scholar 

  67. Calaghan, S.C., White, E., and Le Guennec, J.-Y. (2001). A unifying mechanism for the role of microtubules in the regulation of [Ca2+]i and contraction in the cardiac myocyte. Circ. Res. 89:31e.

    Google Scholar 

  68. Yamamoto, S., Tsutsui, H., Takahashi, M., Ishibashi, Y., Tagawa, H., Imanaka-Yoshida, K., et al. (1998). Role of microtubules in the viscoelastic properties of isolated cardiac muscle. J. Mol. Cell. Cardiol. 30:1841–1853.

    PubMed  CAS  Google Scholar 

  69. Shimoni, Y., Ewart, H.S. and Severson, D. (1999). Insulin stimulation of rat ventricular K+ currents depends on the integrity of the cytoskeleton. J. Physiol. 514.3:735–745.

    PubMed  CAS  Google Scholar 

  70. Maltsev, V.A. and Undrovinas, A.I. (1997). Cytoskeleton modulates coupling between availability and activation of cardiac sodium channel. Am. J. Physiol. Heart Circ. Physiol. 42:H1832-H1840.

    Google Scholar 

  71. Gomez, A.M., Kerfant, B.G., and Vassort, G. (2000). Microtubule disruption modulates Ca(2+) signaling in rat cardiac myocytes. Circ. Res. 86:30–36.

    PubMed  CAS  Google Scholar 

  72. Howarth, F.C., Calaghan, S.C., Boyett, M.R., and White, E. (1999). Effect of the microtubule polymerizing agent taxol on contraction, Ca2+ transient and L-type Ca2+ current in rat ventricular myocytes. J. Physiol. 516:409–419.

    PubMed  CAS  Google Scholar 

  73. Pascarel, C., Brette, F., and Le Guennec, J.-Y. (2001). Enhancement of the T-type calcium current by hyposmotic shock in isolated guinea-pig ventricular myocytes. J. Mol. Cell. Cardiol. 33:1363–1369.

    PubMed  CAS  Google Scholar 

  74. Motlagh, D., Alden, K.J., Russell, B., and Garcia, J. (2002). Sodium current modulation by a tubulin/GTP coupled process in rat neonatal cardiac myocytes. J. Physiol. 540(1):93–103.

    PubMed  CAS  Google Scholar 

  75. Galli, A. and DeFelice, L.J. (1994). Inactivation, of L-type Ca channels in embryonic chick ventricle cells: dependence on the cytoskeletal agents colchicine and taxol. Biophys. J. 67:2296–2304.

    PubMed  CAS  Google Scholar 

  76. Kerfant, B.G., Vassort, G., and Gomez, A.M. (2001). Microtubule disruption by colchicine reversibly enhances calcium signaling in intact rat cardiac myocytes. Circ. Res. 88:E59-E65.

    PubMed  CAS  Google Scholar 

  77. Calaghan, S.C., Le Guennec, J.-Y., and White, E. (2001). Modulation of Ca2+ signaling by microtubule disruption in rat ventricular myocytes and its dependence on the ruptured patch-clamp configuration. Circ. Res. 88:e32-e37.

    PubMed  CAS  Google Scholar 

  78. Unno, T., Komori, S., and Ohashi, H. (1999). Microtubule cytoskeleton involvement in muscarinic suppression of voltage-gated calcium channel current in guinea-pig ileal smooth muscle. Br. J. Pharm. 127:1703–1711.

    CAS  Google Scholar 

  79. Gundersen, G.G. and Cook, T.A. (1999). Microtubules and signal transduction. Curr. Opin. Cell Biol. 11:81–94.

    PubMed  CAS  Google Scholar 

  80. Hayashi M. and Matsumura, F. (1975). Calcium binding to bovine brain tubulin. FEBS Lett. 58:222–225.

    PubMed  CAS  Google Scholar 

  81. Weiss, Y. G., merin, G., Koganov, E., Ribo, A., Oppenheim-Eden, A., Medalion, B., et al. (2000). Postcardio-pulmonary bypass hypoxemia: a prospective study on incidence, risk factors, and clinical significance. J. Cardiothorac. Vasc. Anesth. 14: 506–513.

    PubMed  CAS  Google Scholar 

  82. Pei J.-M., Yu X.-C., Fung, M.-L., Zhou, J.-J., Cheung, C.-S., Wong, N.-S., et al. (2000). Impaired Gsα and adenylyl cyclase cause β-adrenoceptor desensitization in chronically hypoxic rat hearts. Am. J. Physiol. Cell Physiol. 279:C1455-C1463.

    PubMed  CAS  Google Scholar 

  83. Jennings, R.B., Murry, C.E., Steenbergen, J.C., and Reimer, K.A. (1990). Development of cell injury in sustained acute ischemia. Circulation 82:II2-II12.

    PubMed  CAS  Google Scholar 

  84. Kwiatkowska-Patzer, B., Patzer, J.A., and Heller, L.J. (1993). Pseudomonas aeruginosa exotoxin A enhances automaticity and potentiates hypoxic depression of isolated rat hearts. Proc. Soc. Exp. Biol. Med. 202:377–383.

    PubMed  CAS  Google Scholar 

  85. Hein, S., Scheffold, T., and Schaper, J. (1995). Ischemia induces early changes to cytoskeletal and contractile proteins in diseased human myocardium. J. Thorac. Cardiovasc. Surg. 110:89–98.

    PubMed  CAS  Google Scholar 

  86. Iwai, K., Hori, M., Kitabatake, A., Kurihara, H., Uchida, K., Inoue, M., et al. (1990). Disruption of microtubules as an early sign of irreversible ischemic injury. Circ. Res. 67:694–706.

    PubMed  CAS  Google Scholar 

  87. Elsasser, A., Suzuki, K., and Schaper, J. (2000). Unresolved issues regarding the role of apoptosis in the pathogenesis of ischemic injury and heart failure. J. Mol. Cell. Cardiol. 32:711–724.

    PubMed  CAS  Google Scholar 

  88. Bluhm, W.F., Martin, J.L., Mestril, R., and Dillmann, W.H. (1998). Specific heat shock proteins protect microtubules during simulated ischemia in cardiac myocytes. Am. J. Physiol. Heart Circ. Physiol. 275:H2243-H2249.

    CAS  Google Scholar 

  89. Cummings, J., Kaplan, J.L, Gao, E., Clas, D., Dalsey, W.C., and deGaravilla, L. (2000). Antagonism of the cardiodepressant effects of adenosine during acute hypoxia. Acad. Emerg. Med. 7:618–624.

    PubMed  CAS  Google Scholar 

  90. Kronon, M., Allen, B.S., Halldorsson, A., Rahman, S., Wang, T., and Ilbawi, M. (1999). Dose dependency of L-arginine in neonatal myocardial protection: the nitric oxide paradox. J. Thorac. Cardiovasc. Surg. 118:655–664.

    PubMed  CAS  Google Scholar 

  91. Shiono, N., Rao, V., Weisel, R.D., Kawasaki, M., Li, R.-K., Mickle, D.A.G., et al. (2002). l-Arginine protects human heart cells from low-volume anoxia and reoxygenation. Am. J. Physiol. Heart Circ. Physiol. 282:H805-H815.

    PubMed  CAS  Google Scholar 

  92. Eiserich, J.P., Estevez, A.G., Bamberg, T.V., Ye, Y.Z., Chumley, P.H., Beckman, J.S., et al. (1999). Microtubule dysfunction by posttranslational nitrotyrosination of α-tubulin: a nitric oxide-dependent mechanism of cellular injury. Proc. Natl. Acad. Sci. USA 96:6365–6370.

    PubMed  CAS  Google Scholar 

  93. Sato, H., Hori, M., Kitakaze, M., Iwai, K., Takashima, S. Kurihara, H., et al. (1993). Reperfusion after brief ischemia disrupts the microtubule network in canine hearts. Circ. Res. 72:361–375.

    PubMed  CAS  Google Scholar 

  94. Liu, H., Zhang, H.Y., Zhu, X., Shao, Z., and Yao, Z. (2001). Preconditioning blocks cardiocyte apoptosis: role of KATP channels and PKC-ε. Am. J. Physiol. Heart Circ. Physiol. 282:H1380-H1386.

    Google Scholar 

  95. Sharma, A. and Singh, M. (2000). Possible mechanism of cardioprotective effect of ischaemic preconditioning in isolated rat heart. Pharmacol. Res. 41:635–640.

    PubMed  CAS  Google Scholar 

  96. Liu, Y., Ytrehus, K., and Downey, J.M. (1994). Evidence that translocation of protein kinase C is a key event during ischemic preconditioning of rabbit myocardium. J. Mol. Cell. Cardiol. 26:661–668.

    PubMed  CAS  Google Scholar 

  97. Arutunyan, A., Webster, D.R., Swift, L.M., and Sarvazyan, N. (2001). Localized injury in cardiomyocyte network: a new experimental model of ischemia-reperfusion arrhythmias. Am. J. Physiol. Heart Circ. Physiol. 280:H1905-H1915.

    PubMed  CAS  Google Scholar 

  98. Giepmans, B.N.G., Verlaan, I., Hengeveld, T., Janssen, H., Calafat, J., Falk, M.M., et al. (2001). Gap junction protein connexin-43 interacts directly with microtubules. Curr. Biol. 11:1364–1368.

    PubMed  CAS  Google Scholar 

  99. Davis, J.C. Jr. (1999). A practical approach to gout. Postgrad. Med. 106:115–123.

    PubMed  Google Scholar 

  100. Oakley, C.M. (2000). Myocarditis, pericarditis and other pericardial diseases. Heart 84:449–454.

    PubMed  CAS  Google Scholar 

  101. Sullivan, T.P., King, L.E., and Boyd, A.S. (1998). Colchicine in dermatology. J. Am. Acad. Dermatol. 39:993–999.

    PubMed  CAS  Google Scholar 

  102. Simkin, P.J. and Gardner, G.C. (2000). Colchicine use in cyclosporine treated transplant recipients: how little is too much? J. Rheumatol. 27:1334–1337.

    PubMed  CAS  Google Scholar 

  103. Hoffstein, S., Goldstein, I.M., and Weissman, G. (1977). Role of microtubule asembly in lysosomal enzyme secretion from human polymorphonuclear leukocytes. A reevaluation. J. Cell Biol. 73:242–256.

    PubMed  CAS  Google Scholar 

  104. Gregory, R.K. and Smith, I.E. (2000). Vinorelbine—a clinical review. Br. J. Cancer 82:1907–1913.

    PubMed  CAS  Google Scholar 

  105. Supko, J.G., Lynch, T.J., Clark, J.W., Fram, R., Allen, L.F., Velagapudi, R., et al. (2000). A phase 1 clinical and pharmacokinetic study of the dolastatin analogue cemadotin administered as a 5-day continuous intravenous infusion. Cancer Chemother. Pharmacol. 46:319–328.

    PubMed  CAS  Google Scholar 

  106. Rabkin, S.W. and Sunga, P. (1987). The effect of doxorubicin (adriamycin) on cytoplasmic microtubule system in cardiac cells. J. Mol. Cell. Cardiol. 19:1073–1083.

    PubMed  CAS  Google Scholar 

  107. Zhang, C.C., Yang, J.-M., White, E., Murphy, M., Levine, A., and Hait, W.N. (1998). The role of MAP4 expression in the sensitivity to paclitaxel and resistance to vinca alkaloids in p53 mutant cells. Oncogene 16:1617–1624.

    PubMed  CAS  Google Scholar 

  108. Zhang, C.C., Yang, J.-M., Bash-Babula, J., White, E., Murphy, M.D., Levine, A.J., et al. (1999). DNA damage increases sensitivity to vinca alkaloids and decreases sensitivity to taxanes through p53-dependent repression of microtubule-associated protein 4. Cancer Res. 59:3663–3670.

    PubMed  CAS  Google Scholar 

  109. Cainarca, S., Messali, S., Ballabio, A., and Meroni, G. (1999). Functional characterization of the Opitz syndrome gene product (midin): evidence for homodimerization and association with microtubules throughout the cell cycle. Hum. Mol. Genet. 8:1387–1396.

    PubMed  CAS  Google Scholar 

  110. Marszalek, J.R., Ruiz-Lozano, P., Roberts, E., Chien, K.R., and Goldstein, L.S.B. (1999). Situs inversus and embryonic ciliary morphogenesis defects in mouse mutants lacking the KIF3A subunit of kinesin-II. Proc. Natl. Acad. Sci. USA 96:5043–5048.

    PubMed  CAS  Google Scholar 

  111. Hein, S., Kostin, S., Heling, A., Maeno, Y., and Schaper, J. (2000). The role of the cytoskeleton in heart failure. Cardiol. Res. 45:273–278.

    CAS  Google Scholar 

  112. ter Keurs, H.E.D.J. (1998). Microtubules in cardiac hypertrophy. Circ. Res. 82:828–831.

    PubMed  CAS  Google Scholar 

  113. Walsh, R.A. (1997). Microtubules and pressure-overload hypertrophy. Circ. Res. 80:295–296.

    PubMed  CAS  Google Scholar 

  114. Rappaport, L. and Samuel, J.L. (1988). Microtubules in cardiac myocytes. Int. Rev. Cytol. 113:101–143.

    PubMed  CAS  Google Scholar 

  115. Steinberg, S.F. (2000). Many pathways to cardiac hypertrophy. J. Mol. Cell. Cardiol. 32:1381–1384.

    PubMed  CAS  Google Scholar 

  116. Tagawa, H., Koide, M., Sato, H., Zile, M.R., Carabello, B.A. and Cooper, G., IV. (1998). Cytoskeletal role in the transition from compensated to decompensated hypertrophy during adult canine left ventricular pressure overloading. Circ. Res. 82:751–761.

    PubMed  CAS  Google Scholar 

  117. Zile, M.R., Koide, M., Sato, H., Ishiguro, Y., Conrad, C.H., Buckley, J.M., et al. (1999). Role of microtubules in the contractile dysfunction of hypertrophied myocardium. J. Am. Coll. Cardiol. 33:250–260.

    PubMed  CAS  Google Scholar 

  118. Koide, M., Hamawaki, M., Narishige, T., Sato, H., Nemoto, S., DeFreyte, B.S., et al. (2000). Microtubule depolymerization normalizes in vivo myocardial contractile function in dogs with pressure-overload left ventricular hypertrophy. Circulation 102:1045–1052.

    PubMed  CAS  Google Scholar 

  119. Tsutsui, H., Ishibashi, Y., Takahashi, M., Namba, T., Tagawa, H., Imanaka-Yoshida, K., et al. (1999). Chronic colchicine administration attenuates cardiac hypertrophy in spontaneously hypertensive rats. J. Mol. Cell. Cardiol. 31:1203–1213.

    PubMed  CAS  Google Scholar 

  120. Cicogna, A.C., Robinson, K.G., Conrad, C.H., Singh, K., Squire, R., Okoshi, M.P., et al. (1999). Direct effects of colchicine on myocardial function. Studies in hypertrophied and failing spontaneously hypertensive rats. Hypertension 33:60–65.

    PubMed  CAS  Google Scholar 

  121. Bailey, B.A., Dipla, K., Li, S., and Houser, S.R. (1997). Cellular basis of contractile derangements of hypertrophied feline ventricular myocytes. J. Mol. Cell. Cardiol. 29:1823–1835.

    PubMed  CAS  Google Scholar 

  122. Wang, X., Li, F., Campbell, S.E., and Gerdes, A.M. (1999). Chronic pressure overload cardiac hypertrophy and failure in guinea pigs: II. Cytoskeletal remodelling. J. Mol. Cell. Cardiol. 31:319–331.

    PubMed  CAS  Google Scholar 

  123. Collins, J.F., Pawloski-Dahm, C., Davis, M.G., Ball, N., Dorn, II, G.W., and Walsh, R.A. (1996). The role of the cytoskeleton in left ventricular pressure overload hypertrophy and failure. J. Mol. Cell. Cardiol. 28:1435–1443.

    PubMed  CAS  Google Scholar 

  124. Samuel, J.-L., Marotte, F., Delcayre, C., and Rappaport, L. (1986). Microtubule reorganization is related to rate of heart myocyte hypertrophy in rat. Am. J. Physiol. Heart Circ. Physiol. 251:H1118-H1125.

    CAS  Google Scholar 

  125. Stamenovic, D., Mijailovich, S.M., Tolic-Norrelykke, I.M., Chen, J., and Wang, N. (2002). Cell prestress II. Contribution of microtubules. Am. J. Physiol. Cell Physiol. 282:C617-C624.

    PubMed  CAS  Google Scholar 

  126. Tagawa, H., Wang, N., Narishige, T., Ingber, D.E., Zile, M.R., and Cooper, G.I. (1997). Cytoskeletal mechanics in pressure-overload cardiac hypertrophy. Circ. Res. 80:281–289.

    PubMed  CAS  Google Scholar 

  127. Heidemann, S.R., Kaech, S., Buxbaum, R.E., and Matus, A. (1999). Direct observations of the mechanical behaviors of the cytoskeleton in living fibroblasts. J. Cell Biol. 145:109–122.

    PubMed  CAS  Google Scholar 

  128. Kent, R.L., Mann, D.L., Urabe, Y., Hisano, R., Hewett, K.W., Loughnane, M., et al. (1989). Contractile dysfunction of isolated feline cardiocytes in response to viscous loading. Am. J. Physiol. Heart Circ. Physiol. 26:H1717-H1727.

    Google Scholar 

  129. Zile, M.R., Richardson, K., Cowles, M.K., Buckley, J.M., Koide, M., Cowles, B.A., et al. (1998). Constitutive properties of adult ammalian cardiac muscle cells. Circulation 98:567–579.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, 79430, Lubbock, TX

    Daniel R. Webster

Authors
  1. Daniel R. Webster
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniel R. Webster.

Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/s12012-002-0007-2.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Webster, D.R. Microtubules in cardiac toxicity and disease. Cardiovasc Toxicol 2, 75–89 (2002). https://doi.org/10.1385/CT:2:2:075

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1385/CT:2:2:075

Key Words

Search

Navigation