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Thresholds for cellular disruption and activation of the stress response in renal epithelia. Am J Physiol 1999 Aug;277(2):F227-34

Date

08/13/1999

Pubmed ID

10444577

DOI

10.1152/ajprenal.1999.277.2.F227

Scopus ID

2-s2.0-0032830172   38 Citations

Abstract

Renal ischemia causes a rapid fall in cellular ATP, increased intracellular calcium (Ca(i)), and dissociation of Na(+)-K(+)-ATPase from the cytoskeleton along with initiation of a stress response. We examined changes in Ca(i), Na(+)-K(+)-ATPase detergent solubility, and activation of heat-shock transcription factor (HSF) in relation to graded reduction of ATP in LLC-PK(1) cells to determine whether initiation of the stress response was related to any one of these perturbations alone. Ca(i) increased first at 75% of control ATP. Triton X-100 solubility of Na(+)-K(+)-ATPase increased below 70% control ATP. Reducing cellular ATP below 50% control consistently activated HSF. Stepped decrements in cellular ATP below the respective thresholds caused incremental increases in Ca(i), Na(+)-K(+)-ATPase solubility, and HSF activation. ATP depletion activated both HSF1 and HSF2. Proteasome inhibition caused activation of HSF1 and HSF2 in a pattern similar to ATP depletion. Lactate dehydrogenase release remained at control levels irrespective of the degree of ATP depletion. Progressive accumulation of nonnative proteins may be the critical signal for the adaptive induction of the stress response in renal epithelia.

Author List

van Why SK, Kim S, Geibel J, Seebach FA, Kashgarian M, Siegel NJ

Author

Scott K. Van Why MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphate
Animals
Calcium
Cysteine Endopeptidases
DNA-Binding Proteins
Detergents
Differential Threshold
Epithelial Cells
Heat Shock Transcription Factors
Heat-Shock Proteins
Intracellular Membranes
Kidney
L-Lactate Dehydrogenase
LLC-PK1 Cells
Multienzyme Complexes
Octoxynol
Proteasome Endopeptidase Complex
Sodium-Potassium-Exchanging ATPase
Solubility
Stress, Physiological
Swine
Transcription Factors