TY - JOUR
T1 - 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
AU - Venkatachalam, M. A.
AU - Patel, Y. J.
AU - Kreisberg, J. I.
AU - Weinberg, J. M.
PY - 1988
Y1 - 1988
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=0023861035&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0023861035&partnerID=8YFLogxK
U2 - 10.1172/JCI113380
DO - 10.1172/JCI113380
M3 - Article
C2 - 3125228
AN - SCOPUS:0023861035
SN - 0021-9738
VL - 81
SP - 745
EP - 758
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 3
ER -