Document Detail

Energy thresholds that determine membrane integrity and injury in a renal epithelial cell line (LLC-PK1). Relationships to phospholipid degradation and unesterified fatty acid accumulation.
MedLine Citation:
PMID:  3125228     Owner:  NLM     Status:  MEDLINE    
This study related ATP levels with membrane damage, lipid abnormalities, and cell death in energy-depleted LLC-PK1 cells. Oxidative phosphorylation was inhibited by antimycin A, and glycolysis was regulated by graded glucose deprivation to achieve stepwise ATP depletion. Over a range of ATP levels down to approximately equal to 5% of normal, over 5 h, cells were altered only minimally, or injured reversibly. Such cells maintained mitochondrial potential, and retained more K+ than cells without an energy source. Over the same duration, cells without an energy source were lethally injured. Treatment with antimycin induced increments of triglycerides and decreases of phospholipids. With severe ATP depletion (approximately equal to 5-10% of normal after 5 h), decrease of phospholipids was marked. Cells in which ATP was not measurable (or was less than 5% of normal) showed comparable phospholipid declines but, in addition, showed massive and progressive increase of unesterified fatty acids. The results identified a low threshold of ATP, at best 5-10% of normal, which preserved viability in LLC-PK1 cells despite major loss of membrane phospholipids. This threshold also determined the ability of cells to maintain their normally low levels of unesterified fatty acids. Failure of energy-dependent mechanisms that normally metabolize unesterified fatty acids may be a correlate of the extent of energy depletion that determines lethal injury.
M A Venkatachalam; Y J Patel; J I Kreisberg; J M Weinberg
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  81     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1988 Mar 
Date Detail:
Created Date:  1988-04-07     Completed Date:  1988-04-07     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  745-58     Citation Subset:  AIM; IM    
Department of Pathology, University of Texas Health Science Center, San Antonio 78284.
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MeSH Terms
Acetates / metabolism
Adenosine Triphosphate / metabolism
Arachidonic Acid
Arachidonic Acids / metabolism
Cell Line
Cell Membrane / metabolism*,  pathology,  ultrastructure
Cell Survival*
Culture Media
Energy Metabolism*
Fatty Acids, Nonesterified / metabolism*
Fluorescent Dyes
Lactates / metabolism
Lactic Acid
Mitochondria / metabolism
Phospholipids / metabolism*
Potassium / metabolism
Rhodamine 123
Rhodamines / pharmacology
Grant Support
Reg. No./Substance:
0/Acetates; 0/Arachidonic Acids; 0/Culture Media; 0/Fatty Acids, Nonesterified; 0/Fluorescent Dyes; 0/Lactates; 0/Phospholipids; 0/Rhodamines; 50-21-5/Lactic Acid; 506-32-1/Arachidonic Acid; 56-65-5/Adenosine Triphosphate; 62669-70-9/Rhodamine 123; 7440-09-7/Potassium

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

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