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Heat shock protein 60 in rostral ventrolateral medulla reduces cardiovascular fatality during experimental endotoxemia in the rat
Author(s) -
Chang Alice Y.W.,
Chan Samuel H.H.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a470-a
Subject(s) - rostral ventrolateral medulla , cytosol , heat shock protein , hsp60 , mitochondrion , prohibitin , aldh2 , medicine , cytochrome c , biology , microbiology and biotechnology , endocrinology , chemistry , hsp70 , biochemistry , central nervous system , medulla oblongata , gene , aldehyde dehydrogenase , enzyme
We evaluated the hypothesis that the 60‐kDa heat shock protein 60 (HSP60) reduces cardiovascular fatality during experimental endotoxemia via an antiapoptotic action in the rostral ventrolateral medulla (RVLM). In Sprague‐Dawley rats, proteomic or Western blot analysis revealed a progressive augmentation of HSP60 expression in the RVLM after intravenous administration of Escherichia coli lipopolysaccharide. Intriguingly, superimposed on this augmented expression was a progressive decline in mitochondrial, or elevation in cytosolic HSP60 in ventrolateral medulla. Loss‐of‐function manipulations in the RVLM using anti‐HSP60 antiserum or antisense hsp60 oligonucleotide exacerbated mortality by potentiating the cardiovascular depression during experimental endotoxemia, alongside intensified nucleosomal DNA fragmentation, elevated cytoplasmic histone‐associated DNA fragments or augmented cytochrome c /caspase‐3 cascade of apoptotic signaling in the RVLM. Immunoprecipitation coupled with immunoblot analysis further revealed a progressive increase in the complex formed between HSP60 and mitochondrial or cytosolic Bax or mitochondrial Bcl‐2 during endotoxemia, alongside a dissociation of the cytosolic HSP60‐Bcl‐2 complex. We conclude that HSP60 re‐distributed from mitochondrion to cytosol in the RVLM confers neuroprotection against fatal cardiovascular depression during endotoxemia via reduced activation of the cytochrome c /caspase‐3 cascade of apoptotic signaling through enhanced interactions with mitochondrial or cytosolic Bax or Bcl‐2.