Histone-induced damage of a mammalian epithelium: the conductive
effect.
Kleine, Teri J., Amy Gladfelter, Peter N. Lewis, and Simon A. Lewis.
Department of Physiology and Biophysics, University of Texas
Medical Branch, 301 University Blvd., Galveston, TX, 77555-0641, Telephone
Number 409-772-3397, FAX Number 409-772-3381
APStracts 2:0035C, 1995.
Human semen has been reported to be cytotoxic to rat descending colon by a
mechanism involving polyamines (cationic molecules) and collagenase. In this
study we report that histones, cationic proteins found in human semen, can
contribute to semen's cytotoxicity. Histones H1, H4 and H5, when added to the
mucosal-side of rabbit urinary bladder epithelium, were found to alter the
transepithelial conductance (Gt) in a voltage-sensitive manner. When the cell
interior was negative, the conductance rapidly increased and plateaued. When
the cell interior was positive, the induced-conductance decreased to control
values. Histone increased the Gt by increasing the apical membrane
conductance rather than the tight junction conductance. The magnitude of the
Gt increase was dose-dependent, and the histone-induced conductance was non
-selective for sodium, potassium, and chloride. The induced conductance could
be reversed by either increasing mucosal calcium concentration or by removal
of histone from the mucosal solution. Prolonged exposure of the epithelium to
histone was toxic as determined by the irreversible loss of transepithelial
resistance. These results indicate that histone increases membrane ionic
permeability, is cytotoxic, and thus may contribute to human semen's toxic
effect on colonic epithelium.
Received 1 August 1994; accepted in final form 16 November 1994
APS Manuscript Number C0452-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1994 The American Physiological Society.
Published in APStracts on 27 February 1995.