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

Manjeri A Venkatachalam, Yogendra J Patel, J. I. Kreisberg, J. M. Weinberg

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

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 ≃ 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 (≃ 5-10% of normal after 5 h), decrease of phospholipids was marked. Cells in which ATP was not measurable (or was < 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 least 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.

Original languageEnglish (US)
Pages (from-to)745-758
Number of pages14
JournalJournal of Clinical Investigation
Volume81
Issue number3
StatePublished - 1988

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Phospholipids
Fatty Acids
Adenosine Triphosphate
Epithelial Cells
Kidney
Cell Line
Membranes
Wounds and Injuries
LLC-PK1 Cells
Antimycin A
Oxidative Phosphorylation
Glycolysis
Membrane Lipids
Triglycerides
Cell Death
Glucose

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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title = "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",
abstract = "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 ≃ 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 (≃ 5-10{\%} of normal after 5 h), decrease of phospholipids was marked. Cells in which ATP was not measurable (or was < 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 least 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.",
author = "Venkatachalam, {Manjeri A} and Patel, {Yogendra J} and Kreisberg, {J. I.} and Weinberg, {J. M.}",
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AU - Patel, Yogendra J

AU - Kreisberg, J. I.

AU - Weinberg, J. M.

PY - 1988

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AB - 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 ≃ 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 (≃ 5-10% of normal after 5 h), decrease of phospholipids was marked. Cells in which ATP was not measurable (or was < 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 least 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.

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