{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:50:41Z","timestamp":1773291041088,"version":"3.50.1"},"reference-count":63,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,7,6]],"date-time":"2006-07-06T00:00:00Z","timestamp":1152144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2006,7,15]]},"abstract":"<jats:p>The rostral ventrolateral medulla (RVLM) is the origin of a \u2018life\u2010and\u2010death\u2019 signal that reflects central cardiovascular regulatory failure during brain stem death. Using an experimental endotoxaemia model, we evaluated the hypothesis that the 60 kDa heat shock protein 60 (HSP60) reduces cardiovascular fatality during brain stem death via an anti\u2010apoptotic action in the RVLM. In Sprague\u2010Dawley rats maintained under propofol anaesthesia, proteomic or Western blot analysis revealed a progressive augmentation of HSP60 expression in the RVLM after intravenous administration of <jats:italic>Escherichia coli<\/jats:italic> lipopolysaccharide (30 mg kg<jats:sup>\u22121<\/jats:sup>). Pretreatment with a microinjection of actinomycin D or cycloheximide into bilateral RVLM significantly blunted this HSP60 increase, whereas real\u2010time PCR showed progressive augmentation of <jats:italic>hsp60<\/jats:italic> mRNA. Intriguingly, superimposed on the augmented expression was a progressive decline in mitochondrial, or elevation in cytosolic, HSP60 in ventrolateral medulla. Loss\u2010of\u2010function manipulations in the RVLM using anti\u2010HSP60 antiserum or antisense <jats:italic>hsp60<\/jats:italic> oligonucleotide exacerbated mortality by potentiating the cardiovascular depression during experimental endotoxaemia, alongside intensified nucleosomal DNA fragmentation, elevated cytoplasmic histone\u2010associated DNA fragments or augmented cytochrome<jats:italic>c<\/jats:italic>\u2013caspase\u20103 cascade of apoptotic signalling 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\u20102 during endotoxaemia, alongside a dissociation of the cytosolic HSP60\u2013Bcl\u20102 complex. We conclude that HSP60 redistributed from mitochondrion to cytosol in the RVLM confers neuroprotection against fatal cardiovascular depression during endotoxaemia via reduced activation of the cytochrome <jats:italic>c<\/jats:italic>\u2013caspase\u20103 cascade of apoptotic signalling through enhanced interactions with mitochondrial or cytosolic Bax or Bcl\u20102.<\/jats:p>","DOI":"10.1113\/jphysiol.2006.110890","type":"journal-article","created":{"date-parts":[[2006,5,5]],"date-time":"2006-05-05T00:31:23Z","timestamp":1146789083000},"page":"547-564","source":"Crossref","is-referenced-by-count":28,"title":["Heat shock protein 60 in rostral ventrolateral medulla reduces cardiovascular fatality during endotoxaemia in the rat"],"prefix":"10.1113","volume":"574","author":[{"given":"Alice Y. W.","family":"Chang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie Y. 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