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Mitochondrial Dysfunction in Mechanisms of Ethanol Toxicity in the Spinal Neural Crest
Faculty Dissertations
  • Melissa J. Beck, Cedarville University
Date of Award
1-1-2001
Document Type
Dissertation
Degree Name
Doctor of Philosophy (Ph.D.)
Institution Granting Degree
University of Michigan
Cedarville University School or Department
Pharmaceutical Sciences
First Advisor
Craig Harris
Second Advisor
Martin Philbert
Third Advisor
Kathryn Tosney
Keywords
  • Mitochondria,
  • toxicity,
  • toxicology
Subject Categories
Abstract
It was hypothesized that ethanol inhibits neural crest cell (NCC) migration and differentiation through induction of the mitochondrial permeability transition (MPT). Cultures of spinal NCCs contained mixtures of polarized and unpolarized mitochondria. Migration of NCCs was enhanced following establishment of mitochondrial potentials. Most control NCCs either remained undifferentiated or expressed Schwann cell markers. Differentiated cells exhibited greater mitochondrial polarization but lower migration rates than their undifferentiated counterparts. Ethanol decreased mitochondrial transmembrane potential. Ethanol ultimately inhibited NCC migration. Death of NCCs and loss of mitochondrial membrane potential by ethanol was prevented by the MPT inhibitor, bongkrekic acid (BKA), but BKA-pretreatment did not alter Updated 1/12/15 ethanol-induced changes in NCC migration. In utero exposure to ethanol decreased embryonic mitochondrial glutathione but increased embryonic ATP content. These data suggest that the MPT is unrelated to ethanolinduced perturbation of migration. However, MPT pore opening mediates death of undifferentiated NCCs in vitro, and depletion of mitochondrial glutathione may initiate opening of the pore in vivo. The high degree of correlation between mitochondrial polarization states and NCC migration and differentiation suggests that genetic and environmental factors that coordinate NCC function also play a central role in mitochondrial maturation.
Citation Information
Melissa J. Beck. "Mitochondrial Dysfunction in Mechanisms of Ethanol Toxicity in the Spinal Neural Crest" (2001)
Available at: http://works.bepress.com/melissa_beck/75/