Linked Life Data

12236785

Source:http://linkedlifedata.com/resource/pubmed/id/12236785

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2002-9-18
pubmed:abstractText
Heme oxygenase (HO) is a key enzyme in heme metabolism; it oxidatively degrades heme to biliverdin, accompanied by formation of free iron and carbon monoxide. Biliverdin is subsequently reduced by cytosolic biliverdin reductase to form bilirubin, a potent antioxidant. We recently found that tumor cells utilize HO to protect themselves from oxidative stress by producing the antioxidant bilirubin. This result suggested an important potential therapeutic strategy: suppression of bilirubin production with the use of HO inhibitors; hence, cancer cells become vulnerable to oxidative stress induced by anticancer drugs or leukocytes of the host. This concept was validated by using the intraarterial administration of an HO inhibitor, zinc protoporphyrin, in nonphysiological solution. In the present study, zinc protoporphyrin (ZnPP) was conjugated with poly(ethylene glycol) (PEG) with molecular weight of 5000, to make ZnPP, a water-soluble compound (PEG-ZnPP), and to improve its tumor-targeting efficiency. PEG was conjugated to ZnPP through newly introduced amino groups, where ethylenediamine residues were added at C6 and C7 of protoporphyrin. The divalent zinc cation was chelated into the protoporphyrin ring to obtain PEG-ZnPP. PEG-ZnPP did become highly water-soluble, and it formed multimolecular associations with molecules larger than 70 kDa in aqueous media. PEG-ZnPP inhibited splenic microsomal HO activity in vitro in a competitive manner in the presence of hemin, with an apparent inhibitory constant of 0.12 microM. Most important, PEG-ZnPP injected intravenously significantly suppressed intratumor HO activity in a murine solid tumor model, which suggests that tumor-targeted inhibition of HO is possible with the use of PEG-ZnPP.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1043-1802
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1031-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:articleTitle
Pegylated zinc protoporphyrin: a water-soluble heme oxygenase inhibitor with tumor-targeting capacity.
pubmed:affiliation
Department of Microbiology, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't