Irreversible injury in anoxic hepatocytes precipitated by an abrupt increase in plasma membrane permeability.

B. Herman, A. L. Nieminen, G. J. Gores, J. J. Lemasters

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132 Scopus citations

Abstract

Using low-light digitized video microscopy, the onset, progression, and reversibility of anoxic injury were assessed in single hepatocytes isolated from fasted rats. Cell-surface bleb formation occurred in three stages over 1-3 h after anoxia. Stage I was characterized by formation of numerous small blebs. In stage II, small blebs enlarged by coalescence and fusion to form a few large terminal blebs. Near the end of stage II, cells began to swell rapidly, ending with the apparent breakdown of one of the terminal blebs. Breakdown of the bleb membrane initiated stage III of injury and was coincident with a rapid increase of nonspecific permeability to organic cationic and anionic molecules. On reoxygenation, stages I and II were fully reversible, and plasma membrane blebs were resorbed completely within 6 min of reoxygenation without loss of viability. Stage III, however, was not reversible, and no morphological changes occurred on reoxygenation. The results indicate that onset of cell death owing to anoxia is a rapid event initiated by a sudden increase of nonspecific plasma membrane permeability caused by rupture of a terminal bleb. Anoxic injury is reversible until this event occurs.

Original languageEnglish (US)
Pages (from-to)146-151
Number of pages6
JournalThe FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume2
Issue number2
DOIs
StatePublished - Feb 1988

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