The effect of age on the response of the detrusor to intracellular mechanical stimulus: DNA replication and the cell actin matrix

Omer M.A. Karim, Narihito Seki, Kenneth J. Pienta, Jacek L. Mostwin

Research output: Contribution to journalArticle

Abstract

Benign prostatic hypertrophy and posterior urethral valves present at both extremes of the age spectrum. Both disease processes can obstruct the urinary stream and ultimately have pathophysiological effects on detrusor structure and function. The mechanisms regulating the structural reorganization of the detrusor to a mechanical outflow obstruction are not known. In an attempt to identify maturational differences in myoctyte ultrastructure and consequent effects these might have in modifying the response of the destrusor to mechanical stimulus, we studied differences in dyanmic nuclear‐cytoskeletal interactions in detrusor tissue in an animal model. Using a drug which spcifically severs actin, cytochalasin D (CD), as an intracellular mechanical stimulus, we measured changes in nuclear area and the rate of DNA synthesis in detrusor myocytes from young (2–3 wee) and old (8–12 mon) guinea pgis. We found that there were age specific differences to intracellular mechanical stimuli in detrusor muscle. Nuclei of myocytes from young animals showed elastic recoil on severing the cell actin matrix and the tissue from young animals increased replicative DNA synthesis with an intracelluar stimulus. In contrast, nuclear shape changes in myocytes from old animals suggested less elasticity, and there was no increase in DNA synthesis with disruption of the cell actin matrix. Anti‐α‐smooth muscle actin antibody and rhodamine phalloidin staining of actin in cytochalasin D treated primary explants of detrusor mycocytes showed dose dependent disruption of the actin component of the cytoskeleton. These results suggest that there are fundamental modifications in detrusor myocyte ultrastructure with age. These maturational changes might result in differences in the pathophysiological and structural reorganization of the destrusor in response to outflow obstruction in infancy and adulthood. Furthurmore, they suggest that (1) a tensile equilibrium exists between the myocyte nucleus and cytoskeleton; (2) there appears to be a decrease in myocyte nuclear elasticity with ageing; (3)release of nuclear template restrictions increases activity of DNA polymerase α in young, but not old, detrusor myocytes; and (4) mechanico‐chemical signal transduction in detrusor myocytes may be mediated via the cytoskeleton. In addition, based on previous reports of actin within the nucleus, the results suggest that (1) nuclear actin may have a homeostatic structural role, maintaining the tensile equilibrium between nucleus and cytoskeleton, and (2) integrity of nuclear actin may function to maintain the spatial template restriction of DNA polymerase α activity.

Original languageEnglish (US)
Pages (from-to)373-384
Number of pages12
JournalJournal of cellular biochemistry
Volume48
Issue number4
DOIs
StatePublished - Apr 1992

Keywords

  • DNA synthesis
  • cytochalasin D
  • nuclear matrix
  • smooth muscle

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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