Differential expression of myocardial heat shock proteins in rats acutely exposed to fluoride

Abstract

Acute fluoride (F − ) toxicity is known to cause severe cardiac complications and leads to sudden heart failure. Previously, we reported that increased myocardial oxidative damage, apoptosis, altered cytoskeleton and AMPK signaling proteins associated with energy deprivation in acute F − induced cardiac dysfunction. The present study was aimed to decipher the status of myocardial heat shock proteins (HspsHsp27, Hsp32, Hsp40, Hsp60, Hsp70, Hsp90) and heat shock transcription factor 1 (Hsf1) in acute F − -intoxicated rats. In order to study the expression of myocardial Hsps, male Wistar rats were treated with single oral doses of 45 and 90 mg/kg F − for 24 h. The expression levels of myocardial Hsps were determined using RT-PCR, western blotting, and immunohistochemical studies. Acute F − -intoxicated rats showed elevated levels of both the transcripts and protein expression of Hsf1, Hsp27, Hsp32, Hsp60, and Hsp70 when compared to control. In addition, the expression levels of Hsp40 and Hsp90 were significantly declined in a dosedependent fashion in F − -treated animals. Our result suggests that differential expression of Hsps in the rat myocardium could serve as a balance between pro-survival and death signal during acute F − -induced heart failure.

Heat shock protein 60 and cardiovascular diseases: An intricate love‐hate story

“…145 In this model, HSP60 overexpression is suggested to result from increased apoptotic and oxidative events induced by acute Fl − toxicity. 145 Chronic hypersympathetic activity is a frequent finding in HF as indicated by high resting heart rate (HR). In an organ with an already compromised contractility, persistent stimulation by the sympathetic nervous system (SNS) implies increasing the workload the heart is subjected to, and the resulting stress this system is endowed with activates endogenous defense mechanisms, including the HSPs response.…”

“…A dose-dependent increase in both myocardial transcript and protein levels for HSPs and HSF-1 including HSP70, HSP60, HSP32, and HSP27 was reported, while an inverse pattern was observed for HSP40 and HSP90. 145 In this model, HSP60 overexpression is suggested to result from increased apoptotic and oxidative events induced by acute Fl − toxicity. 145 Chronic hypersympathetic activity is a frequent finding in HF as indicated by high resting heart rate (HR).…”

“…Acute fluoride (F − ) toxicity is yet another known event related to acute HF, where cardiovascular impairment is manifested by electrolyte imbalances leading to ventricular arrhythmias, a strong oxidative response with concomitant decrease in its antioxidative counterpart, induction of myocardial apoptosis and necrosis, ATP depletion and cytoskeletal dysfunction. Since HSP expression responds to all of the aforementioned stress‐inducing stimuli, Panneerselvam et al 145 characterized the cardiac expression profile of some of the members of this family of proteins, including HSP27, HSP32, HSP40, HSP60, HSP70, and HSP90, as well as the HSF‐1 transcription factor, in an in vivo rat model of acute Fl − toxicity. A dose‐dependent increase in both myocardial transcript and protein levels for HSPs and HSF‐1 including HSP70, HSP60, HSP32, and HSP27 was reported, while an inverse pattern was observed for HSP40 and HSP90 145 .…”

“…Since HSP expression responds to all of the aforementioned stress‐inducing stimuli, Panneerselvam et al 145 characterized the cardiac expression profile of some of the members of this family of proteins, including HSP27, HSP32, HSP40, HSP60, HSP70, and HSP90, as well as the HSF‐1 transcription factor, in an in vivo rat model of acute Fl − toxicity. A dose‐dependent increase in both myocardial transcript and protein levels for HSPs and HSF‐1 including HSP70, HSP60, HSP32, and HSP27 was reported, while an inverse pattern was observed for HSP40 and HSP90 145 . In this model, HSP60 overexpression is suggested to result from increased apoptotic and oxidative events induced by acute Fl − toxicity 145 …”

The Contribution of Fluoride to the Pathogenesis of Eye Diseases: Molecular Mechanisms and Implications for Public Health

“…In vivo studies using animal models have found that chronic F exposure can modulate the expression of heat shock proteins in cardiac tissue, liver, kidney and testes [ 204 , 205 , 206 ]. Recently, Panneerselvam et al demonstrated that F significantly downregulated the expression of heat shock protein 40 (Hsp40) within living mammalian cells in vivo and upregulated HsP27 and Hsp70 [ 204 ]. Consistent with this, Zhao et al also found that F upregulated mRNA and proteins levels of Hsf27 [ 205 ].…”