Involvement of the heat shock response (HSR) regulatory pathway in cadmium-elicited cerebral damage.

Abstract

The heat shock response (HSR) is a cellular protective mechanism that is characterized by the induction of heat shock transcription factors (HSFs) and heat shock proteins (HSPs) in response to diverse cellular and environmental stressors, including cadmium (Cd). However, little is known about the relationship between the damaging effects of Cd and the HSR pathway in the chicken cerebrum following Cd exposure. To explore whether Cd exposure elicits cerebral damage and triggers the HSR pathway, chicks were exposed to Cd in the daily diet at different concentrations (35, 70, or 140mg/kg feed) for 90days, while a control group was fed the standard diet without Cd. Histopathological examination of cerebral tissue from Cd-exposed chickens showed neuronal damage, as evidenced by swelling and degeneration of neurons, loss of neurons, and capillary damage. Cd exposure significantly increased mRNA expression of HSF1, HSF2, and HSF3, and mRNA and protein expression of three major stress-inducible HSPs (HSP60, HSP70, and HSP90). Moreover, Cd exposure differentially modulated mRNA expression of small HSP (sHSPs), most notably reducing expression of HSP27 (HSPB1). Furthermore, Cd exposure increased TUNEL-positive neuronal apoptotic cells and up-regulated protein expression of caspase-1, caspase-8, caspase-3, and p53, leading to apoptosis. Taken together, these data demonstrate that activation of the HSR and apoptotic pathways by Cd exposure is involved in Cd-elicited cerebral damage in the chicken. Synopsis for the graphical abstract Cadmium (Cd)-induced neuronal damage triggers the heat shock response (HSR) by activating heat shock transcription factors (HSFs) and subsequent induction of major heat shock proteins (notably, HSP60, HSP70, and HSP90). Moreover, Cd exposure activates caspase-1, caspase-8, caspase-3, and p53 protein, thereby resulting in neuronal apoptosis in the chicken brain.