Effects of 12-O-tetradecanoyl-phorbol- 13-acetate on myofibril integrity and Ca2+ content in developing myotubes

J. Croop, G. Dubyak, Y. Toyama, A. Dlugosz, A. Scarpa, H. Holtzer

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

The cocarcinogen 12-O-tetradecanoyl-phorbol-13-acetate (TPA) has a prompt and selective effect on striated myofibrils in well-formed, multinucleated myotubes. The myofibrillar apparatus is totally disrupted and largely degraded after 3 days in TPA. Fluorescent-tagged antibodies to muscle-specific light meromyosin and electron microscopy document this catabolic effect of TPA. This selective degradation of fully assembled striated myofibrils is readily reversible. This reassembly of myofibrils requires de novo protein synthesis. The TPA-treated myotubes are unusually rich in autophagosomes, organelles rarely observed in normal myotubes. TPA has no discernable effect on the morphology of the subsarcolemmal microfilaments, mitochondria, microtubules, or sarcoplasmic reticulum (SR). The programmed disappearance of the fibroblast-type, intermediate 10-nm filaments (FIF) that occurs as normal myotubes mature is not altered by TPA. However, the TPA-treated myotubes depleted of myofibrils are filled with an extensive meshwork of the muscle-type intermediate 10-nm filaments (MIF). The drug has no obvious effect on the constitutive contractile proteins comprising the submembranous microfilaments, or the FIF in presumptive myoblasts or fibroblasts, nor does it affect the motility associated with these replicating cells. The striking increase in total calcium content which occurs as normal myotubes mature is absent in myotubes treated with TPA.

Original languageEnglish (US)
Pages (from-to)460-474
Number of pages15
JournalDevelopmental Biology
Volume89
Issue number2
DOIs
StatePublished - Feb 1982
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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