Neuroprotective role of heat shock protein 70 in the rostral ventrolateral medulla during acute mevinphos intoxication in the rat

Abstract

Heat shock protein (HSP) is a family of highly conserved proteins that respond to stress and participate actively in cytoprotection. Within the HSP family, HSP70 is the major inducible member that confers protection against cell death. This study investigated whether HSP70 plays a neuroprotective role at the rostral ventrolateral medulla (RVLM), the origin of sympathetic neurogenic vasomotor tone in the medulla oblongata where the organophosphate insecticide mevinphos (Mev) acts to elicit cardiovascular toxicity. Experiments were carried out in adult male Sprague-Dawley rats that were maintained under propofol anesthesia. Intravenous administration of Mev (960 microg/kg) induced a significant increase in the HSP70 level in the ventrolateral medulla during phase I ('pro-life' phase), and returned to baseline during phase II ('pro-death' phase) Mev intoxication. Compared to artificial cerebrospinal fluid, normal mouse serum (1:20), or sense hsp70 oligonucleotide (50 pmol) pretreatment, microinjection of an anti-HSP70 antiserum (1:20) or an antisense hsp70 oligonucleotide (50 pmol) bilaterally into the RVLM significantly increased mortality, shortened the duration of phase I intoxication and augmented the induced hypotension in rats that received Mev (960 microg/ kg, i.v.). These results suggest that HSP70 induced in the RVLM during Mev intoxication provides neuroprotection against the organophosphate poison via prevention of cardiovascular depression.

Hypobaric hypoxia preconditioning attenuates acute lung injury during high-altitude exposure in rats via up-regulating heat-shock protein 70

“…The neuroprotective role of HSP70 in the rat brain has been studied previously by using an anti-HSP70 Ab (antibody) [20,21]. A neutralizing polyclonal rabbit anti-(mouse HSP70) Ab (0.2 mg/kg of body weight; SPA-812E; Assay Designs) dissolved in non-pyrogenic sterile saline was injected intravenously 24 h prior to simulated HAE.…”

Pro-life role for c-Jun N-terminal kinase and p38 mitogen-activated protein kinase at rostral ventrolateral medulla in experimental brain stem death

“…In addition to transcriptional regulation, c-Jun also mediates posttranscriptional modification on HIF-1α by protecting it from proteasomal degradation [66]. Interestingly, all these proteins have been found to play a pro-life role in RVLM in our experimental model of brain stem death [16,67-71]. Fischer et al, [72] reported that marked increases in JNK and p38MAPK activity, coincident with an increase in phosphorylation of c-Jun and ATF-2, can be detected as early as 15–30 min after rapid changes in hemodynamic load in Wistar rats.…”

Taurine Amino Acids and Brain Development: A Review

“…Anti-inflammatory, anti-oxidative, and anti-apoptotic qualities make taurine neuroprotective. Taurine inhibits pro-inflammatory cytokines and chemokines in activated microglia and astrocytes, reducing neuroinflammation (Chang et al, 2015).…”

“…Taurine protects neurones in animal models of Alzheimer's, Parkinson's, Huntington's, and multiple sclerosis (Wu et al, 2016). Taurine reduces amyloid-beta deposition and neuroinflammatory reactions in animal models of Alzheimer's disease, improving cognition (Chang et al, 2015). Taurine improves motor deficits and dopaminergic neurone loss in animal models of Parkinson's disease (Wu et al, 2016).…”