Browse > Article
http://dx.doi.org/10.5125/jkaoms.2010.36.5.346

The effect of heat shock protein 70 on inducible nitric oxide synthase during sepsis in rats  

Lee, Yong-Keun (Department of Oral and Maxillofacial Surgery, School of Dentistry, Institute of Oral Bioscience, Brain Korea 21 project, Chonbuk National University)
Ahn, Yung (Department of Oral and Maxillofacial Surgery, School of Dentistry, Institute of Oral Bioscience, Brain Korea 21 project, Chonbuk National University)
Leem, Dae-Ho (Department of Oral and Maxillofacial Surgery, School of Dentistry, Institute of Oral Bioscience, Brain Korea 21 project, Chonbuk National University)
Baek, Jin-A (Department of Oral and Maxillofacial Surgery, School of Dentistry, Institute of Oral Bioscience, Brain Korea 21 project, Chonbuk National University)
Ko, Seung-O (Department of Oral and Maxillofacial Surgery, School of Dentistry, Institute of Oral Bioscience, Brain Korea 21 project, Chonbuk National University)
Shin, Hyo-Keun (Department of Oral and Maxillofacial Surgery, School of Dentistry, Institute of Oral Bioscience, Brain Korea 21 project, Chonbuk National University)
Publication Information
Journal of the Korean Association of Oral and Maxillofacial Surgeons / v.36, no.5, 2010 , pp. 346-352 More about this Journal
Abstract
Introduction: Heat shock protein70 (HSP70) is a highly conserved family of proteins produced after a variety of stresses. Many studies reported that the overexpression of HSP70 can improve the prognosis of the patients with sepsis through a reduction of the nitric oxide concentration. However, these results only revealed the effect of HSP70 and nitric oxide. No studies have examined the relationship between HSP70 and nitric oxide. The aim of this study was to evaluate the effect of the overexpression of HSP70 on the expression of inducible nitric oxide synthase and the nitric oxide concentration. In addition, the mechanism of the relationship of HSP70 and inducible nitric oxide synthase (iNOS) in sepsis was examined. Materials and Methods: The experiments were performed on male sprague-dawley rats. Sepsis was induced by a cecal ligation and puncture (CLP). Glutamine (GLN) or saline was administered 1 hour after the initiation of sepsis. Serum and lung tissues were acquired from the rats 12 hours or 24 hours after the initiation of sepsis. The nitric oxide concentration, the expression of HSP70 in lung, and the gene expression of iNOS in lung were analyzed. The three groups, sham operation, CLP and CLP+GLN, were compared. Results: Compared to the other groups, in CLP+GLN, GLN administered after the initiation of sepsis enhanced the expression of HSP70 in the lung at 12 hours ($47.19{\pm}10.04$ vs. $33.22{\pm}8.28$, P=0.025) and 24 hours ($47.06{\pm}10.60$ vs. $31.90{\pm}4.83$, P=0.004). In CLP+GLN, GLN attenuated the expression of iNOS messenger RNA (mRNA) in the lung at 12 hours ($5,513.73{\pm}1,051.60$ vs. $4,167.17{\pm}951.59$, P=0.025) and 24 hours ($18,740.27{\pm}8,241.20$ vs. $9,437.65{\pm}2,521.07$, P=0.016), and reduced the concentration of nitric oxide in the serum at 12 hours ($0.86{\pm}0.48$ vs. $3.82{\pm}2.53$, P=0.016) and 24 hours ($0.39{\pm}0.25$ vs. $1.85{\pm}1.70$, P=0.025). Conclusion: The overexpression of HSP70 induced by the administration of GLN in sepsis attenuates the expression of the iNOS gene but reduces the nitric oxide concentration.
Keywords
Heat shock proteins; inducible nitric oxide synthase (iNOS); Nitric oxide (NO); Sepsis;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Kellum JA, Johnson JP, Kramer D, Palevsky P, Brady JJ, Pinsky MR. Diffusive vs. convective therapy: effects on mediators of inflammation in patients with severe systemic inflammatory response syndrome. Crit Care Med 1998;26:1995-2000.   DOI   ScienceOn
2 McMaster P, Shann F. The use of extracorporeal techniques to remove humoral factors in sepsis. Pediatric Crit Care Med 2003; 4:2-7.   DOI   ScienceOn
3 Sigal LH. Molecular biology and immunology for clinicians 18: Heat shock proteins/chaperonins. J Clin Rheumatol 2002;8:174- 80.   DOI   ScienceOn
4 Sumioka I, Matsura T, Kai M, Yamada K. Potential roles of hepatic heat shock protein 25 and 70i in protection of mice against acetaminophen-induced liver injury. Life Sci 2004; 74: 2551-61.   DOI   ScienceOn
5 Singleton KD, Serkova N, Beckey VE, Wischmeyer PE. Glutamine attenuates lung injury and improves survival after sepsis: role of enhanced heat shock protein expression. Crit Care Med 2005;33:1206-13.   DOI   ScienceOn
6 Dellinger RP. Cardiovascular management of septic shock. Crit Care Med 2003;31:946-55.   DOI   ScienceOn
7 Pinsky MR. Dysregulation of the immune response in severe sepsis. Am J Med Sci 2004;328:220-9.   DOI   ScienceOn
8 Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, et al. Effect of treatment with low doses of hydrocortisone and fluorocortisone on mortality in patients with septic shock. JAMA 2002;288:862-71.   DOI   ScienceOn
9 Kiang JG. Inducible heat shock protein 70 kD and inducible nitric oxide synthase in hemorrhage/resuscitation-induced injury. Cell Res 2004;14:450-9.   DOI   ScienceOn
10 Su F, Nguyen ND, Wang Z, Cai Y, Rogiers P, Vincent JL. Fever control in septic shock: beneficial or harmful? Shock 2005;23: 516-20.
11 Sanli A, Onen A, Sarioglu S, Sis B, Guneli E, Gokcen B, et al. Glutamine administration enhances the healing of lung parenchymal injuries and reduces air leakage in rats. Tohoku J Exp Med 2006;210:239-45.   DOI   ScienceOn
12 Cohen J, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004; 32:858-73.   DOI   ScienceOn
13 Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368-77.   DOI   ScienceOn
14 Rhodes A, Bennett ED. Early-goal directed therapy: an evidencebased review. Crit Care Med 2004;32(11 Suppl):S448-50.
15 Thiemermann C, Szabo′C, Mitchell JA, Vane JR. Vascular hyporeactivity to vasoconstrictor agents and hemodynamic decompensation in hemorrhagic shock is mediated by nitric oxide. Proc Natl Acad Sci U S A 1993;90:267-71.   DOI   ScienceOn
16 Aranow JS, Zhuang J, Wang H, Larkin V, Smith M, Fink MP. A selective inhibitor of inducible in nitric oxide synthase prolongs survival in a rat model of bacterial peritonitis: comparison with two nonselective strategies. Shock 1996;5:116-21.   DOI
17 Tandara AA, Kloeters O, Kim I, Mogford JE, Mustoe TA. Age effect on HSP70: decreased resistance to ischemic and oxidative stress in HDF. J Surg Res 2006;132:32-9.   DOI   ScienceOn
18 Grover R, Zaccardelli D, Colice G, Guntupalli K, Watson D, Vincent JL. An open-label dose escalation study of the nitric oxide synthase inhibitor NG-methyl-arginine hydrochloride (546C88) in patients with septic shock. Crit Care Med 1999;27:913-22.   DOI   ScienceOn
19 Watson D, Grover R, Anzueto A, Lorente J, Smithies M, Bellomo R, et al. Cardiovascular effects of the nitric oxide synthase inhibitor NG-methyl-L-arginine hydrochloride (546C88) in patients with septic shock: results of a randomized, double-blind, placebo-controlled multicenter study (study no. 144-002). Crit Care Med 2004;32:13-20.   DOI   ScienceOn
20 Ritossa FA. A new puffing pattern induced by temperature shock and DNP in Drosophillia. Experientia 1962;18:571-3.   DOI   ScienceOn
21 Opal SM, Fisher CJ Jr, Dhainaut JF, Vincent JL, Brase R, Lowry SF, et al. Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double-blind, placebocontrolled, multicenter trial. The Interleukin-1 Receptor Aantagonist Sepsis Investigator Group. Crit Care Med 1997;25: 1115-24.&   DOI   ScienceOn
22 Wenzel RP. Treating sepsis. N Engl J Med 2002;347:966-7. .   DOI   ScienceOn
23 Wheeler AP, Bernard GR. Treating patients with severe sepsis. N Engl J Med 1999;340:207-14.   DOI   ScienceOn
24 Cole L, Bellomo R, Hart G, Journois D, Davenport P, Tipping P, et al. A phase II randomized, controlled trial of continuous hemofiltration in sepsis. Crit Care Med 2002;30:100-6.   DOI   ScienceOn
25 Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001; 344:699-709.   DOI   ScienceOn
26 Corrigan JJ Jr. Heparin therapy in bacterial septicemia. J Pediatr 1977;91:695-700.   DOI
27 Abraham E, Anzueto A, Gutierrez G, Tessler S, San Pedro G, Wunderink R, et al. Double-blind randomized controlled trial of monoclonal antibody to human tumour necrosis factor in treatment of septic shock. NORASEPT II Study Group. Lancet 1998;351:929-33.
28 Sander A, Armbruster W, Sander B, Daul AE, Lange R, Peters J. Hemofiltration increases IL-6 clearance in early systemic inflammatory response syndrome but dose not alter IL-6 and TNF-$\alpha$ plasma concentrations. Intensive Care Med 1997;23:878-84.   DOI   ScienceOn
29 Braun N, Rosenfeld S, Giolai M, Banzhaf W, Fretschner R, Warth H. Effects of continuous hemodiafiltration on IL-6, TNFalpha, C3a and TCC in patients with SIRS/septic shock using two different membranes. Contrib Nephrol 1995;116:89-98.
30 Dong HP, Chen HW, Hsu C, Chiu HY, Lin LC, Yang RC. Previous heat shock treatment attenuates lipopolysaccharide-induced hyporesponsiveness of platelets in rats. Shock 2005;24: 239-44.   DOI   ScienceOn
31 Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001;29:1303-10.   DOI   ScienceOn
32 Augus DC, Wax RS. Epidemiology of sepsis: an update. Crit Care Med 2001;29(7 Suppl):S109-16.
33 Cohen RI, Wilson D, Liu SF. Nitric oxide modifies the sarcoplasmic reticular calcium release channel in endotoxemia by both guanosine-3', 5'(cyclic) phosphate-dependent and independent pathways. Crit Care Med 2006;34:173-81.   DOI   ScienceOn
34 O'Brien JM Jr, Abraham E. New approaches to the treatment of sepsis. Clin Chest Med 2003;24:521-48.   DOI   ScienceOn
35 Holmes CL, Russell JA, Walley KR. Genetic polymorphisms in sepsis and septic shock: role in prognosis and potential for therapy. Chest 2003;124:1103-15.   DOI   ScienceOn
36 Chen HW, Hsu C, Lu TS, Wang SJ, Yang RC. Heat shock pretreatment prevents cardiac mitochondrial dysfunction during sepsis. Shock 2003;20:274-9.   DOI   ScienceOn
37 Cariou A, Vinsonneau C, Dhainaut JF. Adjunctive therapies in sepsis: an evidence-based review. Crit Care Med 2004;32(11 Suppl):S562-70.
38 Opal SM, Gluck T. Endotoxin as a drug target. Crit Care Med 2003;31(1 Suppl): 57-64.
39 Kim DJ, Park SH, Sheen MR, Jeon US, Kim SW, Koh ES, et al. Comparison of experimental lung injury from acute renal failure with injury due to sepsis. Respiration 2006;73:815-24.   DOI   ScienceOn
40 Doruk N, Buyukakilli B, Atici S, Cinel I, Cinel L, Tamer L, et al. Oral The effect of preventive use of alanyl-glutamine on diaphragm muscle function in cecal ligation and puncture-induced sepsis model. JPEN J Parenter Enteral Nutr 2005;29:36-43.   DOI   ScienceOn
41 Torres-Duen ?s D, Benjamim CF, Ferreira SH, Cunha FQ. Failure of neutrophil migration to infectious focus and cardiovascular changes on sepsis in rats: effects of the inhibition of nitric oxides production, removal of infectious focus, and antimicrobial treatment. Shock 2006;25:267-76.   DOI   ScienceOn
42 Masuda Y, Sumita S, Fujimura N, Namiki A. Geranylgeranylacetone attenuates septic diaphragm dysfunction by induction of heat shock protein 70. Crit Care Med 2003;31:2585-91.   DOI   ScienceOn
43 Li PL, Chao YM, Chan SH, Chan JY. Potentiation of baroreceptor reflex response by heat shock protein 70 in nucleus tractus solitarii confers cardiovascular protection during heatstroke. Circulation 2001;103:2114-9.   DOI   ScienceOn
44 Yang RC, Yang SL, Chen SW, Lai SL, Chen SS, Chiang CS. Previous heat shock treatment attenuates bicuculline-induced convulsions in rats. Exp Brain Res 1996;108:18-22.
45 Nakada J, Matsura T, Okazaki N, Nishida T, Togawa A, Minami Y, et al. Oral administration of geranylgeranylacetone improves survival rate in a rat endotoxin shock model: administration timing and heat shock protein 70 induction. Shock 2005;24:482-7.   DOI   ScienceOn
46 Yang SL, Jing SH, Chen SS, Chen TJ, Yang RC. The effect of hyperthermic treatment on electroencephalographic recovery after interruption of respiration in rats. Exp Brain Res 1994;99:431-4.