Expression pattern of heme oxygenase isoenzymes 1 and 2 in normal and stress-exposed rat liver.
Heme oxygenase (HO) catalyzes the oxidative cleavage of the alpha-mesocarbon of Fe-protoporphyrin-IX yielding equimolar amounts of biliverdin-IXa, iron, and carbon monoxide. The HO-system consists of two isoenzymes, namely HO-2 and the inducible isoform HO-1, also referred to as heat shock protein (hsp) 32. Although both parenchymal and non-parenchymal liver cells participate in heme metabolism, the expression pattern of the isoenzymes in normal and stress exposed liver is unknown. To study this, rats underwent either endotoxin (lipopolysaccharide [LPS]) challenge, hemorrhagic hypotension, glutathione (GSH) depletion, or cobalt chloride injection, all known to provoke oxidative stress. HO-2 messenger RNA (mRNA) and protein were constitutively expressed in hepatocytes, Kupffer/endothelial-, and stellate (Ito-) cell enriched fractions. Although both non-parenchymal cell fractions expressed HO-1 transcripts, HO-1 immunoreactive protein was restricted to Kupffer cells in the normal liver. In contrast to HO-2, a significant increase in HO-1 on the whole organ level was noted by hemorrhagic hypotension, GSH depletion, and cobalt chloride injection. However, the distinct stress models led to a strikingly different cell-type specific and sublobular expression pattern of HO-1 gene expression. HO-1 was inducible in sinusoidal lining cells (hemorrhagic hypotension, LPS challenge), in periportal (cobalt chloride), or pericentral (GSH depletion, hemorrhagic hypotension) hepatocytes. The blockade of protein translation before hemorrhage by cycloheximide reduced upregulation of HO-1/hsp32 mRNA significantly (65.4% reduction, P < .05), whereas the inducibility of hsp70 transcript was maintained. In addition to transcriptional regulation, HO-1 seems to be subject to posttranscriptional control in particular in non-parenchymal cells.
Bauer
I
I
Klinik für Anästhesiologie und Intensivmedizin der Universität des Saarlandes, Homburg/Saar, FRG.
Wanner
G A
GA
Rensing
H
H
Alte
C
C
Miescher
E A
EA
Wolf
B
B
Pannen
B H
BH
Clemens
M G
MG
Bauer
M
M
D000818:Animals; D003035:Cobalt / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D007527:Isoenzymes; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D003035:Cobalt; D006419:Heme Oxygenase (Decyclizing); C018021:cobaltous chloride