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Hyperbilirubinemia protects against focal ischemia in rats
Author(s) -
Kitamura Yoshihisa,
Ishida Yuji,
Takata Kazuyuki,
Mizutani Hiroto,
Kakimura Junichi,
Inden Masatoshi,
Nakata Junko,
Taniguchi Takashi,
Tsukahara Tetsuya,
Akaike Akinori,
Shimohama Shun
Publication year - 2002
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10514
Subject(s) - biliverdin , neuroprotection , heme , biliverdin reductase , bilirubin , heme oxygenase , mutant , chemistry , oxidative stress , ischemia , pharmacology , biochemistry , biology , endocrinology , medicine , enzyme , gene
Heme oxygenase‐1 (HO1) catalyzes oxidation of the heme molecule in concert with NADPH‐cytochrome P450 reductase following the specific cleavage of heme into carbon monoxide, iron, and biliverdin, which is rapidly metabolized to bilirubin. HO1 is a stress‐inducible protein that protects cells against oxidative injury, but its protective mechanism is not fully understood. The Eizai hyperbilirubinemic rat (EHBR), a mutant strain derived from the Sprague‐Dawley rat (SDR), has a mutation in the gene for the canalicular multispecific organic anion transporter, which results in a phenotype of hyperbilirubinemia, and thus is a model of Dubin‐Johnson syndrome in humans. In this study, we compared EHBR and SDR with regard to neuronal death induced by 2 hr of occlusion of the middle cerebral artery and reperfusion. In EHBR, the area that was immunoreactive for microtubule‐associated protein‐2 was significantly reduced, and the HO1‐immunoreactive area was smaller than that in SDR. These results suggest that bilirubin has essentially a neuroprotective effect against focal ischemia and may participate in HO1‐induced neuroprotection. © 2002 Wiley‐Liss, Inc.