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

  • Original Paper
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Journal of Biomedical Science

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 µg/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 sensehsp70 oligonucleotide (50 pmol) pretreatment, microinjection of an anti-HSP70 antiserum (1:20) or an anti-sensehsp70 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 µg/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.

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References

  1. Balali-Mood M, Shariat M. Treatment of organophosphate poisoning. Experience of nerve agents and acute pesticide poisoning on the effects of oximes. J Physiol 92:375–378;1998.

    Google Scholar 

  2. Bardin PG, van Eeden SF. Organophosphate poisoning: grading the severity and comparing treatment between atropine and glycopyrrolate. Crit Care Med 18:956–960;1990.

    PubMed  Google Scholar 

  3. Bardin PG, van Eeden SF, Moolman JA, Foden AP, Joubert JR. Organophosphate and carbamate poisoning. Arch Intern Med 154:1433–1441;1994.

    Article  PubMed  Google Scholar 

  4. Beckmann RP, Mizzen LE, Welch WJ. Interaction of Hsp70 with newly synthesized proteins: implications for protein folding and assembly. Science 248:850–854;1990.

    PubMed  Google Scholar 

  5. Benjamin IJ, McMillan DR. Stress (heat shock) proteins molecular chaperones in cardiovascular biology and disease. Circ Res 83:117–132;1998.

    PubMed  Google Scholar 

  6. Chan JYH, Chan SHH, Chang AYW. Differential contributions of NOS isoforms in the rostral ventrolateral medulla to cardiovascular responses associated with mevinphos intoxication in the rat. Neuropharmacology 46:1184–1194;2004.

    Article  PubMed  Google Scholar 

  7. Chan SHH, Chang KF, Ou CC, Chan JYH. Up-regulation of glutamate receptors in nucleus tractus solitarii underlies potentiation of baroreceptor reflex by heat shock protein 70. Mol Pharmacol 61:1097–1104;2002.

    Article  PubMed  Google Scholar 

  8. Chan SHH, Wang LL, Wang SH, Chan JYH. Differential cardiovascular responses to blockade of nNOS or iNOS in rostral ventrolateral medulla of the rat. Br J Pharmacol 133:606–614;2001.

    PubMed  Google Scholar 

  9. Chang AYW, Chan JYH, Chan SHH. Differential distribution of nitric oxide synthase isoforms in the rostral ventrolateral medulla of the rat. J Biomed Sci 10:285–291;2003.

    PubMed  Google Scholar 

  10. Chang AYW, Chan JYH, Kao FJ, Huang CM, Chan SHH. Engagement of inducible nitric oxide synthase at the rostral ventrolateral medulla during mevinphos intoxication in the rat. J Biomed Sci 8:475–483;2001.

    Google Scholar 

  11. Chuang FR, Jang SW, Lin JL, Chern MS, Chen JB, Hsu KT: QTc prolongation indicates a poor prognosis in patients with organophosphate poisoning. Am J Emerg Med 14:451–453;1996.

    Article  PubMed  Google Scholar 

  12. Eichler J, Silman I. The activity of an endoplasmic reticulum-localized pool of acetylcholinesterase is modulated by heat shock. J Biol Chem 270:4466–4472;1995.

    Article  PubMed  Google Scholar 

  13. Feinstein DL, Galea E, Aquino DA, Li GC, Xu H, Reis DJ. Heat shock protein 70 suppresses astroglial-inducible nitric oxide synthase expression by decreasing NFκB activation. J Biol Chem 271:17724–17732;1996.

    Article  PubMed  Google Scholar 

  14. Fink AL. Chaperone-mediated protein folding. Physiol Rev 79:425–449;1999.

    PubMed  Google Scholar 

  15. Fox A, Castillon K. Employee exposure to mevinphos — an organophosphate pesticide. Appl Occup Environ Hyg 16:506–508;2001.

    Article  PubMed  Google Scholar 

  16. Hauser GJ, Dayao EK, Wasserloos K, Pitt BR, Wong HR. HSP induction inhibits iNOS mRNA expression and attenuates hypotension in endotoxin-challenged rats. Am J Physiol 271:H2529-H2535;1996.

    PubMed  Google Scholar 

  17. Huang CC, Chan SHH, Hsu KS. cGMP/protein kinase G-dependent potentiation of glutamatergic transmission induced by nitric oxide in immature rat rostral ventrolateral medulla neurons in vitro. Mol Pharmacol 64:521–532;2003.

    Article  PubMed  Google Scholar 

  18. Huang CC, Chan SHH, Hsu KS. 3-Morpholinylsydnonimine inhibits glutamatergic transmission in rat rostral ventrolateral medulla via peroxynitrite formation and adenosine release. Mol Pharmacol, in press.

  19. Kuo TBJ, Yang CCH, Chan SHH. Selective activation of vasomotor component of SAP spectrum by nucleus reticularis ventrolateralis in rats. Am J Physiol 272:H485-H492;1997.

    PubMed  Google Scholar 

  20. Lallement G, Baubichon D, Clarencon D, Galonnier M, Peoc'h M, Carpentier P. Review of the value of gacyclidine (GK-11) as adjuvant medication to conventional treatments of organophosphate poisoning: primate experiments mimicking various scenarios of military or terrorist attack by soman. Neurotoxicology 20:675–684;1999.

    PubMed  Google Scholar 

  21. Li PL, Chao YM, Chan SHH, Chan JYH. Potentiation of baroreceptor reflex response by heat shock protein 70 in nucleus tractus solitarii confers cardiovascular protection during heatstroke. Circulation 103:2114–2119;2001.

    PubMed  Google Scholar 

  22. Lindquist S, Craig EA. The heat-shock proteins. Annu Rev Genet 22:631–677;1988.

    Article  PubMed  Google Scholar 

  23. McCauley LA, Rischitelli G, Lambert WE, Lasarev M, Sticker DL, Spencer PS. Symptoms of Gulf War veterans possibly exposed to organophosphate chemical warfare agents at Khamisiyah, Iraq. Int J Occup Environ Health 7:79–89;2001.

    PubMed  Google Scholar 

  24. Morimoto R, Santoro MG. Stress-inducible responses and heat shock protein: new pharmacologic targets for cytoprotection. Nat Biotechnol 16:833–838;1998.

    Article  PubMed  Google Scholar 

  25. Nelson RJ, Ziegelhoffer JR, Nicolet C, Werner-Washburne M, Craig EA. The translation machinery and 70 kd heat shock protein cooperate in protein synthesis. Cell 71:97–105;1992.

    Article  PubMed  Google Scholar 

  26. Robertson JD, Datta K, Biswal SS, Kehrer JP. Heat-shock protein 70 antisense oligomers enhance proteasome inhibitor-induced apoptosis. Biochem J 344:477–485;1999.

    Article  PubMed  Google Scholar 

  27. Ross CA, Ruggiero DA, Park DH, Joh TH, Sved AF, Fernandez-Pardal J, Saavedra JM, Reis DJ. Tonic vasomotor control by the rostral ventrolateral medulla: effect of electrical or chemical stimulation of the area containing C1 adrenaline neurons on arterial pressure, heart rate, and plasma catecholamines and vasopressin. J Neurosci 4:474–494;1984.

    PubMed  Google Scholar 

  28. Sharp FR, Massa SM, Swanson RA. Heat-shock protein protection. Trends Neurosci 22:97–99;1999.

    Article  PubMed  Google Scholar 

  29. Tafuri J, Roberts J. Organophosphate poisoning. Ann Emerg Med 16:193–202;1987.

    Article  PubMed  Google Scholar 

  30. Takahashi H, Kojima T, Ikeda T, Tsuda S, Shirasu Y. Differences in the mode of lethality produced through intravenous and oral administration of organophosphorus insecticides in rats. Fundam Appl Toxicol 16:459–468;1991.

    Article  PubMed  Google Scholar 

  31. Welch WJ. Mammalian stress response: cell physiology, structure/function of stress proteins, and implications for medicine and disease. Physiol Rev 72:1063–1081;1992.

    PubMed  Google Scholar 

  32. Yang CH, Shyr MH, Kuo TBJ, Tan PPC, Chan SHH. Effects of propofol on nociceptive response and power spectra of electroencephalographic and systemic arterial pressure signals in the rat: correlation with plasma concentration. J Pharmacol Exp Ther 275:1568–1574;1995.

    PubMed  Google Scholar 

  33. Yen DHT, Chan JYH, Tseng HP, Huang CI, Lee CH, Chan SHH, Chang AYW. Depression of mitochondrial respiratory enzyme activity in rostral ventrolateral medulla during acute mevinphos intoxication in the rat. Shock 21:358–363;2004.

    Article  PubMed  Google Scholar 

  34. Yen DHT, Yen JC, Len WB, Wang LM, Lee CH, Chan SHH. Spectral changes in systemic arterial pressure signals during acute mevinphos intoxication in the rat. Shock 15:35–41;2001.

    PubMed  Google Scholar 

  35. Yen DHT, Yien HW, Wang LM, Lee CH, Chan SHH. Spectral analysis of systemic arterial pressure and heart rate signals of patients with acute respiratory failure induced by severe organophosphate poisoning. Crit Care Med 28:2805–2811;2000.

    PubMed  Google Scholar 

  36. Yenari MA, Fink SL, Sun GH, Chang LK, Patel MK, Kunis DM, Onley D, Ho DY, Sapolsky RM, Steinberg GK. Gene therapy with HSP72 is neuroprotective in rat models of stroke and epilepsy. Ann Neurol 44:584–591;1998.

    Article  PubMed  Google Scholar 

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Chang, C., Chang, A.Y.W. & Chan, S.H.H. Neuroprotective role of heat shock protein 70 in the rostral ventrolateral medulla during acute mevinphos intoxication in the rat. J Biomed Sci 11, 748–755 (2004). https://doi.org/10.1007/BF02254359

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  • DOI: https://doi.org/10.1007/BF02254359

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