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The Role of Heat Shock Proteins at the Rostral Ventrolateral Medulla in Experimental Endotoxemia in the Rat

Heat shock proteins (HSPs) are abundantly produced in cells that are under stress or injury by acting as a chaperone or promoting folding, unfolding, packing, degradation or denaturing of proteins or peptides. This study evaluated the role of HSP60, HSP70 or HSP90 in the rostral ventrolateral medulla (RVLM), in experimental endotoxemia in the rat.
Adult, male Sprague-Dawley rats maintained by i.v. infusion propofol (25 mg/kg/h) were used. During experimental endotoxemia induced by intravenous administration of E. coli lipopolysaccharide (LPS, 30 mg/kg; serotype 0111:B4), the power density of the vasomotor component of systemic arterial pressure (SAP) spectrum underwent a decrease (Phase I), followed by an increase (Phase II; ¡§pro-life¡¨) and a secondary decrease (Phase III; ¡§pro-death¡¨). Western blot analysis revealed that HSP60 expression in the RVLM was significantly increased during Phase II and Phase III endotoxemia; and HSP70 expression was maximally increased during Phase II. HSP90 protein expression in the RVLM was not significantly changed during endotoxemia.
We further studied the role of HSP60, HSP70 or HSP90 at the RVLM in experimental endotoxemia by pretreating animals with bilaterally microinjection of an anti-HSP serum (HSPAb, 1:20), normal mouse serum, antisense oligodeoxynucleotide (hsp AODN, 50 pmol), sense oligodeoxynucleotide (hsp SODN) or scrambled AODN (hsp SC). Pretreatment with HSP60Ab or hsp60 AODN resulted in significantly higher mortality, shorter survival time and shorter Phase II duration. In addition, the augmented power density of the vasomotor component of SAP signals during Phase II endotoxemia was significantly reduced. Even more detrimental effects were obtained on local application of HSP70Ab or hsp70 AODN into the RVLM. Pretreatment with HSP90Ab or hsp90 AODN was ineffective.
We conclude that the expression of HSP60 and HSP70 in the RVLM may play a ¡§pro-life¡¨ role in fatal experimental endotoxemia; and HSP90 may not be involved.

Identiferoai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0730103-161503
Date30 July 2003
CreatorsLi, Chia-Hsin
ContributorsSamuel H.H. Chan, Po-Wu Gean, Alice Y. W. Chang, Kuei-Sen Hsu, Julie Y.H. Chan
PublisherNSYSU
Source SetsNSYSU Electronic Thesis and Dissertation Archive
LanguageCholon
Detected LanguageEnglish
Typetext
Formatapplication/pdf
Sourcehttp://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0730103-161503
Rightswithheld, Copyright information available at source archive

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