The stress response is initiated in energy deprived renal epithelia coordinate with disruption of cell architecture including loss of Na/K-ATPase attachment to the cytoskeleton; HSP-72 elaboration coincides with cellular restitution. Assessing putative cytoprotective effects of the heat shock proteins (HSPs) in injured kidney has been confounded by the cellular stress used to pre-induce the HSPs. We examined whether HSPs could be pharmacologically induced in renal epithelia and whether prior HSP induction would protect against cellular injury from ATP depletion.
Confluent LLC-PK1cells were treated with Herbimycin A(H), geldanamycin (G) or vehicle for a 2 hour interval (treatment) followed by replacement with normal media for 6 hours (elaboration period). At the end of the elaboration period, the cells were energy deprived for 4 hours by replacement of the growth media with substrate free media and Antimycin A. Gel retardation assays indicated that both H and G caused marked activation of heat shock transcription factor (HSF) by the end of the treatment interval. At the end of the 6 hour elaboration period, Western analysis showed that both H and G induced the cytosolic 70 kD HSPs (HSP-72 and HSC-73). Neither compound altered cellular ATP levels nor disrupted membrane protein-cytoskeleton interactions, as assayed by detergent solubility of Na/K-ATPase, when HSF was activated or when the 70 kD HSPs (HSP-70) were induced. Both H and G, then, initiated the stress response without causing evident cellular injury.
Pre-treated cells were then subjected to metabolic inhibition to determine whether HSP-70 induction by H or G was associated with cytoprotection as manifested by prevention of the cellular ATP depletion or Na/K-ATPase solubilization typical of energy deprived cells. Neither compound altered the rapidity nor depth or ATP depletion from metabolic inhibition. However, prior treatment with H and G prevented solubilization of Na/K-ATPase in cells subjected to 4 hours ATP depletion. Therefore, HSP-70 levels can be pharmacologically enhanced in renal epithelia and prior HSP-70 induction is associated with cytoprotection that is not attributable to preservation of cellular energy. One action of HSP-70, then, may be to stabilize membrane and cytoskeletal protein interactions in metabolically deprived renal epithelia.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Van Why, S., Atasever, B., Neagu, M. et al. Non-Injurious Stress Protein Induction Protects ATP Depleted Renal Epithelia† 1846. Pediatr Res 43 (Suppl 4), 315 (1998). https://doi.org/10.1203/00006450-199804001-01869
Issue Date:
DOI: https://doi.org/10.1203/00006450-199804001-01869