J Korean Assoc Oral Maxillofac Surg.  2010 Oct;36(5):346-352.

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

• Lee YK
• Ahn Y
• Leem DH
• Baek JA
• Ko SO
• Shin HK

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+/-10.04 vs. 33.22+/-8.28, P=0.025) and 24 hours (47.06+/-10.60 vs. 31.90+/-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+/-1,051.60 vs. 4,167.17+/-951.59, P=0.025) and 24 hours (18,740.27 +/-8,241.20 vs. 9,437.65+/-2,521.07, P=0.016), and reduced the concentration of nitric oxide in the serum at 12 hours (0.86+/-0.48 vs. 3.82+/-2.53, P=0.016) and 24 hours (0.39+/-0.25 vs. 1.85+/-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.

Keyword

Heat shock proteins; inducible nitric oxide synthase (iNOS); Nitric oxide (NO); Sepsis

MeSH Terms

Animals
Gene Expression
Glutamine
Heat-Shock Proteins
Hot Temperature
HSP70 Heat-Shock Proteins
Humans
Ligation
Lung
Male
Nitric Oxide
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Prognosis
Proteins
Punctures
Rats
Rats, Sprague-Dawley
RNA, Messenger
Salicylamides
Sepsis
Shock
Glutamine
HSP70 Heat-Shock Proteins
Heat-Shock Proteins
Nitric Oxide
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Proteins
RNA, Messenger
Salicylamides

Figure

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  Fig. 1. NO concentration 12 hours after CLP. (NO: nitric oxide, CLP: cecal ligation and puncture, SHAM: Sham operation, GLN: glutamine, *: P<0.05 compared with SHAM, CLP+GLN)

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  Fig. 2. NO concentration 24 hours after CLP. (NO: nitric oxide, CLP: cecal ligation and puncture, SHAM: Sham operation, GLN: glutamine, *: P<0.05 compared with SHAM, CLP+GLN)

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  Fig. 3. iNOS mRNA in lung 12 hours after CLP. (iNOS: inducible nitric oxide synthase, mRNA: messenger RNA, CLP: cecal ligation and puncture, SHAM: Sham operation, GLN: glutamine, *: P<0.05 compared with SHAM, CLP+GLN)

• 

  Fig. 4. iNOS mRNA in lung 24 hours after CLP. (iNOS: inducible nitric oxide synthase, mRNA: messenger RNA, CLP: cecal ligation and puncture, SHAM: Sham operation, GLN: glutamine, *: P<0.05 compared with SHAM, CLP+GLN)

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  Fig. 5. HSP70 in lung 12 hours after CLP. (HSP: heat shock protein, CLP: cecal ligation and puncture, SHAM: Sham operation, GLN: glutamine, *: P<0.05 compared with SHAM, CLP)

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  Fig. 6. HSP70 in lung 24 hours after CLP. (HSP: heat shock protein, CLP: cecal ligation and puncture, SHAM: Sham operation, GLN: glutamine, *: P<0.05 compared with SHAM, CLP)

Reference

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