Multiparameter digitized video microscopy of toxic and hypoxic injury in single cells

J. J. Lemasters, Gregory James Gores, A. L. Nieminen, T. L. Dawson, B. E. Wray, B. Herman

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

There is no clear picture of the critical events that lead to the transition from reversible to irreversible injury. Many studies have suggested that a rise in cytosolic free Ca2+ initiates plasma membrane bleb formation and a sequence of events that lead ultimately to cell death. In recent studies, we have measured changes in cytosolic free Ca2+, mitochondrial membrane potential, cytosolic pH, and cell surface blebbing in relation to the onset of irreversible injury and cell death following anoxic and toxic injury to single hepatocytes by using multiparameter digitized video microscopy (MDVM). MDVM is an emerging new technology that permits single living cells to be labeled with multiple probes whose fluorescence is responsive to specific cellular parameters of interest. Fluorescence images specific for each probe are collected over time, digitized, and stored. Image analysis and processing then permits quantitation of the spatial distribution of the various parameters with the single living cells. Our results indicate the following: The formation of plasma membrane blebs accompanies all types of injury in hepatocytes. Cell death is a rapid event initiated by rupture of a plasma membrane bleb, and it is coincident with the onset of irreversible injury. An increase of cytosolic free Ca2+ is not the stimulus for bleb formation or the final common pathway leading to cell death. A decrease of mitochondrial membrane potential precedes the loss of cell viability. Cytosolic pH falls by more than 1 pH unit during chemical hypoxia. This acidosis protects against the onset of cell death.

Original languageEnglish (US)
Pages (from-to)83-94
Number of pages12
JournalEnvironmental Health Perspectives
Volume84
StatePublished - 1990
Externally publishedYes

Fingerprint

Video Microscopy
Poisons
Cell death
Blister
microscopy
Microscopic examination
Cell Death
membrane
Cell membranes
Wounds and Injuries
Mitochondrial Membrane Potential
Cells
Cell Membrane
plasma
Hepatocytes
fluorescence
Fluorescence
probe
Membranes
hypoxia

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Public Health, Environmental and Occupational Health

Cite this

Lemasters, J. J., Gores, G. J., Nieminen, A. L., Dawson, T. L., Wray, B. E., & Herman, B. (1990). Multiparameter digitized video microscopy of toxic and hypoxic injury in single cells. Environmental Health Perspectives, 84, 83-94.

Multiparameter digitized video microscopy of toxic and hypoxic injury in single cells. / Lemasters, J. J.; Gores, Gregory James; Nieminen, A. L.; Dawson, T. L.; Wray, B. E.; Herman, B.

In: Environmental Health Perspectives, Vol. 84, 1990, p. 83-94.

Research output: Contribution to journalArticle

Lemasters, JJ, Gores, GJ, Nieminen, AL, Dawson, TL, Wray, BE & Herman, B 1990, 'Multiparameter digitized video microscopy of toxic and hypoxic injury in single cells', Environmental Health Perspectives, vol. 84, pp. 83-94.
Lemasters, J. J. ; Gores, Gregory James ; Nieminen, A. L. ; Dawson, T. L. ; Wray, B. E. ; Herman, B. / Multiparameter digitized video microscopy of toxic and hypoxic injury in single cells. In: Environmental Health Perspectives. 1990 ; Vol. 84. pp. 83-94.
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