Kiang JG, Bowman PD, Wu BW, Hampton N, Kiang AG, Zhao B, Juang
YT, Atkins JL, Tsokos GC.
Geldanamycin treatment inhibits hemorrhage-induced increases
in KLF6 and iNOS expression in un-resuscitated mouse organs:
Role of inducible HSP-70.
J Appl Physiol. 2004 Apr 16
Department of Cellular Injury, Division of Military Casualty
Research, Walter Reed Army Institute of Research, Silver Spring,
MD 20910-7500, USA.
Juliann.Kiang@na.amedd.army.mil
The aim of this study was to determine whether hemorrhage
affects the levels of a variety of stress-related proteins and
whether changes can be inhibited by drugs reported to provide
protection from ischemia and reperfusion injury. Male Swiss
Webster mice were subjected to a 40% hemorrhage without
resuscitation. Western blot analysis indicated that c-Jun (an
AP-1 protein), Kruppel-like factor 6 (KFL6), and inducible
nitric oxide synthase (iNOS) were upregulated sequentially in
that order. Pretreatment of mice with geldanamycin (GA) 16 h
before hemorrhage effectively inhibited the expression of the
proteins KLF6 and iNOS, whereas caffeic acid phenethyl ester did
not. GA pretreatment increased inducible heat shock protein (HSP)
70 but not HSP90 in both sham and hemorrhagic tissues. The
overexpressed inducible HSP70 formed complexes with KLF6 and
iNOS. These results suggest that GA may be therapeutically
useful for reducing hemorrhage-induced injury when used as a
presurgical treatment or when added to resuscitation fluids.
PMID: 15090481
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