Expression of the Constitutive and Inducible Forms of Heat Shock Protein 70 in Human Proximal Tubule Cells Exposed to Heat, Sodium Arsenite, and CdCl 2

Abstract

We determined the expression of the constitutive (hsc 70) and inducible (hsp 70) forms of heat shock protein 70 mRNA and protein in human proximal tubule (HPT) cells exposed to lethal and sublethal concentrations of Cd(+2) under both acute and extended conditions of exposure. The HPT cells exhibited the classic heat shock response when subjected to a physical (heat) or chemical stress (sodium arsenite); hsc 70 mRNA and protein levels were constant or slightly increased, whereas hsp 70 mRNA and protein were greatly elevated. Acute exposure to 53.4 microM CdCl(2) for 4 hr failed to increase either hsc 70 mRNA or protein, a finding similar to that observed under classic conditions of stress. However, under identical conditions of acute exposure to Cd(2+), the expected increase in hsp 70 protein level was suppressed as compared to that found under classic conditions of physical or chemical stress. The decrease in hsp 70 protein level correlated to the reduced expression of mRNA from the hsp 70B gene. The expression of mRNA from the hsp 70A and hsp 70C genes was similar to that found when the cells were treated with heat shock or sodium arsenite. We modeled an extended exposure to Cd(2+) by treating the cells continuously with Cd(2+) at both lethal and sublethal levels over a 16-day time course. Chronic exposure to Cd(2+) failed to increase either hsc 70 mRNA or protein levels in the HPT cells at a nonlethal dosage level and decreased hsc 70 mRNA and protein levels late in the time course of lethal exposure. Under identical conditions, the expression of hsp 70 protein remained at basal levels that were only marginally detectable throughout the time course. Hsp 70A and hsp 70C mRNA levels were unaltered by extended exposure to Cd(2+), and hsp 70B mRNA was not detected during the 16-day time course. Cd(2+) is a poor inducer of hsc 70 and hsp 70 in the proximal tubule under both acute and long-term exposure. These results reinforce the fact that the expression of hsp 70 protein does not result from the transcription of a single gene, but is derived from what may be a complex interplay of several underlying genes.

Mammalian orthoreovirus infection is enhanced in cells pre-treated with sodium arsenite

“…The efficiency of mRNA translation is increased in the presence of supplemental recombinant Hsc70 and the rate of translation elongation may be regulated by chaperone availability [44]. Treatment with SA also increases Hsc70/Hsp70 chaperone levels in cells [45]. Furthermore, Hsc70 is required for HRI activation and blockade of Hsc70 disrupts HRI activation [7].…”

Mammalian orthoreovirus infection is enhanced in cells pre-treated with sodium arsenite

“…The efficiency of mRNA translation is increased in the presence of supplemental recombinant Hsc70 and the rate of translation elongation may be regulated by chaperone availability [44]. Treatment with SA also increases Hsc70/Hsp70 chaperone levels in cells [45]. Furthermore, Hsc70 is required for HRI activation and blockade of Hsc70 disrupts HRI activation [7].…”

Stress response of heavy metal mixture present in wastewater and leachate on heat-shock protein 47-transfected cells

“…4), which is below the World Health Organization (WHO) guidelines level of 4.8 Â 10 À2 mM (10 mg/L) [38]. Previously, Somji et al [39] reported that Cd 2þ is a poor stress response inducer of HSP 70 in human proximal tubule cells under both acute and long-term exposure. On the other hand, more recent results by Lui et al [40] have shown the endoplasmic reticulum (ER) stress response in renal epithelial cells following exposure to 10 mM Cd.…”

Presence of antibody against the inducible Hsp71 in patients with acute heat-induced illness

“…Transgenic expression of the human inducible Hsp70 in a mouse model reduced the extent of damage in hippocampal neurons following permanent middle cerebral artery occlusion (Plumier et al 1997). Harmful conditions such as exposure to mercury, CdCl 2 , heat stress, and osmotic stress also induce Hsps in the kidneys, and some Hsps may have protective functions against these stresses (Gagnon et al 1999;Somji et al 1999;Beck et al 2000;Goering et al 2000).…”

Mammalian orthoreovirus infection is enhanced in cells pre-treated with sodium arsenite

“…The efficiency of mRNA translation is increased in the presence of supplemental recombinant Hsc70 and the rate of translation elongation may be regulated by chaperone availability [44]. Treatment with SA also increases Hsc70/Hsp70 chaperone levels in cells [45]. Furthermore, Hsc70 is required for HRI activation and blockade of Hsc70 disrupts HRI activation [7].…”

Stress response of heavy metal mixture present in wastewater and leachate on heat-shock protein 47-transfected cells

“…4), which is below the World Health Organization (WHO) guidelines level of 4.8 Â 10 À2 mM (10 mg/L) [38]. Previously, Somji et al [39] reported that Cd 2þ is a poor stress response inducer of HSP 70 in human proximal tubule cells under both acute and long-term exposure. On the other hand, more recent results by Lui et al [40] have shown the endoplasmic reticulum (ER) stress response in renal epithelial cells following exposure to 10 mM Cd.…”

Presence of antibody against the inducible Hsp71 in patients with acute heat-induced illness

“…Transgenic expression of the human inducible Hsp70 in a mouse model reduced the extent of damage in hippocampal neurons following permanent middle cerebral artery occlusion (Plumier et al 1997). Harmful conditions such as exposure to mercury, CdCl 2 , heat stress, and osmotic stress also induce Hsps in the kidneys, and some Hsps may have protective functions against these stresses (Gagnon et al 1999;Somji et al 1999;Beck et al 2000;Goering et al 2000).…”

Mammalian orthoreovirus infection is enhanced in cells pre-treated with sodium arsenite

“…The efficiency of mRNA translation is increased in the presence of supplemental recombinant Hsc70 and the rate of translation elongation may be regulated by chaperone availability [44]. Treatment with SA also increases Hsc70/Hsp70 chaperone levels in cells [45]. Furthermore, Hsc70 is required for HRI activation and blockade of Hsc70 disrupts HRI activation [7].…”

Stress response of heavy metal mixture present in wastewater and leachate on heat-shock protein 47-transfected cells

“…4), which is below the World Health Organization (WHO) guidelines level of 4.8 Â 10 À2 mM (10 mg/L) [38]. Previously, Somji et al [39] reported that Cd 2þ is a poor stress response inducer of HSP 70 in human proximal tubule cells under both acute and long-term exposure. On the other hand, more recent results by Lui et al [40] have shown the endoplasmic reticulum (ER) stress response in renal epithelial cells following exposure to 10 mM Cd.…”

Presence of antibody against the inducible Hsp71 in patients with acute heat-induced illness

“…Transgenic expression of the human inducible Hsp70 in a mouse model reduced the extent of damage in hippocampal neurons following permanent middle cerebral artery occlusion (Plumier et al 1997). Harmful conditions such as exposure to mercury, CdCl 2 , heat stress, and osmotic stress also induce Hsps in the kidneys, and some Hsps may have protective functions against these stresses (Gagnon et al 1999;Somji et al 1999;Beck et al 2000;Goering et al 2000).…”