PubMed:8728315 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/8728315","sourcedb":"PubMed","sourceid":"8728315","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/8728315","text":"Interaction of a recombinant form of apolipoprotein[a] with human fibroblasts and with the human hepatoma cell line HepG2.\nWe have studied the binding, uptake, and degradation of a recombinant form of apolipoprotein[a] (r-apo[a]) using a cultured cell model. In HepG2 cells and in human fibroblasts, r-apo[a] complexed with low density lipoprotein(LDL) is bound and internalized via high affinity (Kd = 10 nM) receptors; in both cell types, low affinity (Kd = 200-300 nM) sites also mediate free apo[a] uptake. Using competition studies, we found that the high affinity binding component corresponds to the LDL receptor. Involvement of the LDL receptor in r-apo[a] uptake by fibroblasts was confirmed using fibroblasts derived from an individual homozygous for familial hypercholesterolemia; in contrast to normal fibroblasts, these cells lacked the high affinity r-apo[a] binding component. Cell association of 125I-labeled r-apo[a] was increased and decreased concomitantly with the up- and down-regulation of the LDL receptor in response to a number of compounds. The addition of alpha 2-macroglobulin as well as treatment with heparinase, chondroitinase ABC, and sodium chlorate did not decrease total specific binding of r-apo[a], suggesting that neither the low density lipoprotein receptor-related protein nor cell surface proteoglycans are involved in r-apo[a] clearance. The low affinity binding component present in both fibroblasts and HepG2 cells likely corresponds to the plasminogen receptor, as binding of r-apo[a] to these sites was specifically decreased by the addition of plasminogen or the lysine analogue epsilon-aminocaproic acid, but not by the addition of tissue-type plasminogen activator. Heparin abolished uptake of r-apo[a] by the LDL receptor component only; this indicates that apo[a] must be associated with LDL to be cleared by this receptor. In contrast, free apo[a] can be effectively cleared by the plasminogen receptor which may represent a significant route of clearance for free apo[a] in vivo.","tracks":[{"project":"performance-test","denotations":[{"id":"PD-UBERON-AE-B_T1","span":{"begin":1680,"end":1686},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"}],"attributes":[{"subj":"PD-UBERON-AE-B_T1","pred":"source","obj":"performance-test"}]},{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":37,"end":53},"obj":"gene:4018"},{"id":"T1","span":{"begin":97,"end":105},"obj":"disease:C0023903"},{"id":"T2","span":{"begin":37,"end":53},"obj":"gene:4018"},{"id":"T3","span":{"begin":97,"end":105},"obj":"disease:C2239176"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"},{"subj":"T2","pred":"source","obj":"DisGeNET"},{"subj":"T3","pred":"source","obj":"DisGeNET"}]},{"project":"sentences","denotations":[{"id":"TextSentencer_T1","span":{"begin":0,"end":122},"obj":"Sentence"},{"id":"TextSentencer_T2","span":{"begin":123,"end":258},"obj":"Sentence"},{"id":"TextSentencer_T3","span":{"begin":259,"end":510},"obj":"Sentence"},{"id":"TextSentencer_T4","span":{"begin":511,"end":620},"obj":"Sentence"},{"id":"TextSentencer_T5","span":{"begin":621,"end":891},"obj":"Sentence"},{"id":"TextSentencer_T6","span":{"begin":892,"end":1066},"obj":"Sentence"},{"id":"TextSentencer_T7","span":{"begin":1067,"end":1379},"obj":"Sentence"},{"id":"TextSentencer_T8","span":{"begin":1380,"end":1714},"obj":"Sentence"},{"id":"TextSentencer_T9","span":{"begin":1715,"end":1874},"obj":"Sentence"},{"id":"TextSentencer_T10","span":{"begin":1875,"end":2032},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":122},"obj":"Sentence"},{"id":"T2","span":{"begin":123,"end":258},"obj":"Sentence"},{"id":"T3","span":{"begin":259,"end":510},"obj":"Sentence"},{"id":"T4","span":{"begin":511,"end":620},"obj":"Sentence"},{"id":"T5","span":{"begin":621,"end":891},"obj":"Sentence"},{"id":"T6","span":{"begin":892,"end":1066},"obj":"Sentence"},{"id":"T7","span":{"begin":1067,"end":1379},"obj":"Sentence"},{"id":"T8","span":{"begin":1380,"end":1714},"obj":"Sentence"},{"id":"T9","span":{"begin":1715,"end":1874},"obj":"Sentence"},{"id":"T10","span":{"begin":1875,"end":2032},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"TextSentencer_T1","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T2","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T3","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T4","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T5","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T6","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T7","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T8","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T9","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T10","pred":"source","obj":"sentences"},{"subj":"T1","pred":"source","obj":"sentences"},{"subj":"T2","pred":"source","obj":"sentences"},{"subj":"T3","pred":"source","obj":"sentences"},{"subj":"T4","pred":"source","obj":"sentences"},{"subj":"T5","pred":"source","obj":"sentences"},{"subj":"T6","pred":"source","obj":"sentences"},{"subj":"T7","pred":"source","obj":"sentences"},{"subj":"T8","pred":"source","obj":"sentences"},{"subj":"T9","pred":"source","obj":"sentences"},{"subj":"T10","pred":"source","obj":"sentences"}]},{"project":"UBERON-AE","denotations":[{"id":"PD-UBERON-AE-B_T1","span":{"begin":1680,"end":1686},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"}],"attributes":[{"subj":"PD-UBERON-AE-B_T1","pred":"source","obj":"UBERON-AE"}]},{"project":"DisGeNet-2017-sample","denotations":[{"id":"T743","span":{"begin":640,"end":652},"obj":"gene:3949"},{"id":"T744","span":{"begin":761,"end":790},"obj":"disease:C0020445"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T743","obj":"T744"},{"id":"R2","pred":"associated_with","subj":"T743","obj":"T744"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T743","pred":"source","obj":"DisGeNet-2017-sample"},{"subj":"T744","pred":"source","obj":"DisGeNet-2017-sample"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"performance-test","color":"#eca093","default":true},{"id":"DisGeNET","color":"#939fec"},{"id":"sentences","color":"#b9ec93"},{"id":"UBERON-AE","color":"#ec93d3"},{"id":"DisGeNet-2017-sample","color":"#93ecea"}]}]}}