Document Detail

N-acetylcysteine impairs survival of luteal cells through mitochondrial dysfunction.
MedLine Citation:
PMID:  20151456     Owner:  NLM     Status:  MEDLINE    
N-acetylcysteine (NAC) is known as an antioxidant and used for mucus viscosity reduction. However, this drug prevents or induces cell death depending on the cell type. The response of steroidogenic luteal cells to NAC is unknown. Our data shows that NAC can behave as an antioxidant or prooxidant in dependency on the concentration and mitochondrial energization. NAC elevated the flowcytometric-measured portion of hypodiploid (dying) cells. This rise was completely abolished by aurintricarboxylic acid, an inhibitor of topoisomerase II. NAC increased the secretion of nitric oxide and cellular nitrotyrosine. An image analysis indicated that cells pretreated with NAC and loaded with DHR showed a fluorescent structure probably elicited by the oxidative product of DHR, rhodamine 123 that sequesters mitochondrially. Pretreating luteal cells with NAC or adding NAC directly to mitochondrial fractions followed by assessing the mitochondrial transmembrane potential difference (Deltapsi) by the JC-1 technique demonstrated a marked decrease in Deltapsi. A protonophore restored Deltapsi and rotenone (an inhibitor of respiratory chain complex I) inhibited mitochondrial recovering. Thus, in steroidogenic luteal cells from healthy mature corpus luteum, NAC impairs cellular survival by interfering with mitochondrial metabolism. The protonophore-induced recovering of NAC-provoked decrease in Deltapsi indicates that an ATP synthase-favored route of H(+) re-entry to the matrix is essentially switched off by NAC while other respiratory chain complexes remain intact. These data may be important for therapeutic timing of treatments with NAC. (c) 2010 International Society for Advancement of Cytometry.
Berthold L?hrke; Jinxian Xu; Joachim M Weitzel; Burkhard Kr?ger; Tom Goldammer; Torsten Viergutz
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cytometry. Part A : the journal of the International Society for Analytical Cytology     Volume:  77     ISSN:  1552-4930     ISO Abbreviation:  Cytometry A     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-25     Completed Date:  2010-06-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101235694     Medline TA:  Cytometry A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  310-20     Citation Subset:  IM    
Research Institute for the Biology of Farm Animals, Dummerstorf, Germany.
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MeSH Terms
Acetylcysteine / pharmacology*
Aurintricarboxylic Acid / metabolism
Biological Markers / metabolism
Cell Nucleus / drug effects,  metabolism
Cell Survival / drug effects
Flow Cytometry
Intracellular Space / drug effects,  metabolism
Lipid Peroxides / metabolism
Luteal Cells / cytology*,  drug effects*,  metabolism
Membrane Potential, Mitochondrial / drug effects
Mitochondria / drug effects*,  metabolism*,  pathology
Molecular Imaging
Oxidation-Reduction / drug effects
Progesterone / secretion
Reactive Oxygen Species / metabolism
Rhodamines / metabolism
Signal Transduction / drug effects
Steroids / biosynthesis
Time Factors
Tyrosine / analogs & derivatives,  metabolism
Reg. No./Substance:
0/Biological Markers; 0/Lipid Peroxides; 0/Reactive Oxygen Species; 0/Rhodamines; 0/Steroids; 109244-58-8/dihydrorhodamine 123; 3604-79-3/3-nitrotyrosine; 4431-00-9/Aurintricarboxylic Acid; 55520-40-6/Tyrosine; 57-83-0/Progesterone; 616-91-1/Acetylcysteine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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