Linked Life Data

8663134

Source:http://linkedlifedata.com/resource/pubmed/id/8663134

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
1996-8-20
pubmed:abstractText
Exposure to various forms of oxidative stress (H2O2 and O2.-) significantly increased the intracellular degradation of both "short-lived" and "long-lived" cellular proteins in the human hematopoietic cell line K562. Oxidatively modified hemoglobin and superoxide dismutase used as purified proteolytic substrates were also selectively degraded by K562 cell lysates, but exposure of these protein substrates to very high hydrogen peroxide concentrations actually decreased their proteolytic susceptibility. Our studies found little or no change in the overall capacity of cells and cell lysates to degrade "foreign" oxidized proteins after treatment of K562 cells with hydrogen peroxide or paraquat, a finding supported by proteasome Western blots and unchanged capacity of cell lysates to degrade the fluorogenic peptide succinyl-leucine-leucine-valine-tyrosine-4-methylcoumarin-7-amide. Six days of daily treatment of K562 cells with an antisense oligodeoxynucleotide directed against the initiation codon region of the human proteasome C2 subunit gene dramatically depressed hydrogen peroxide-induced degradation of metabolically radiolabeled intracellular proteins. The actual amount of proteasome in antisense-treated K562 cells was also severely depressed, as revealed by Western blots and by measurements of the degradation of the fluorogenic peptide succinyl-leucine-leucine-valine-tyrosine-4-methylcoumarin-7-amide. The degradation of oxidatively modified foreign protein substrates was also markedly depressed in lysates prepared from K562 cells treated with the proteasome C2 antisense dideoxynucleotide. The inhibitor profile for the degradation of H2O2-modified hemoglobin by K562 cell lysates was consistent with a major role for the ATP-independent 20 S "core" proteasome complex. We conclude that proteasome, probably the 20 S core proteasome complex, is primarily responsible for the selective degradation of oxidatively damaged proteins in human hematopoietic cells. Since "oxidative marking" of cellular proteins by lipoxygenase has been proposed as an important step in red blood cell maturation, it is important to determine which protease or proteases could recognize and degrade such modified substrates. Our results provide evidence that proteasome can, indeed, conduct such selective degradation and appears to be the major cellular protease capable of fulfilling such a role in maturation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
271
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15504-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Degradation of oxidized proteins in K562 human hematopoietic cells by proteasome.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, The Albany Medical College, Albany New York 12208, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't