Induction of the 70 kDa heat shock protein stress response inhibits autophagy: possible consequences for pregnancy outcome

Aim: The induction of heat shock protein synthesis and activation of autophagy are intracellular processes stimulated under adverse conditions. We evaluated the relationship between intracellular concentrations of the inducible 70kDa heat shock protein (hsp70) and autophagy induction in human peripheral blood mononuclear cells (PBMCs) following exposure to sera from pregnant and non-pregnant women.Methods: Autophagy was induced in PBMCs by incubation for 48h with sera from 42 pregnant women at mid-gestation and 45 non-pregnant women. Intracellular concentrations of hsp70 and p62 were measured by ELISA. p62 is a cytoplasmic protein that is consumed during autophagy induction. Its concentration in the cytoplasm is inversely proportional to the extent of autophagy induction (high p62=low autophagy).Results: The p62 concentration was highly correlated with the hsp70 level utilizing sera from both pregnant (Spearman r=0.4731, p=0.0015) and non-pregnant (Spearman r=0.6214, p<0.0001) women. Median p62 (7.4ng/ml versus 2.7ng/ml, p<0.0001) and hsp70 (7.0ng/ml versus 3.5ng/ml, p=0.0022) levels were higher when PBMCS were incubated with sera from pregnant women.Conclusion: The extent of autophagy in PBMCs is inversely proportional to the intracellular hsp70 concentration and sera from pregnant women induces hsp70 and inhibits autophagy to a greater extent than does sera from non-pregnant women. A stress response that induces hsp70 has the potential to interfere with autophagy-related events.