Reference - Detail
| RRC ID | 39881 |
|---|---|
| Author | Takahashi Y, Takahashi S, Shiga Y, Yoshimi T, Miura T. |
| Title | Hypoxic induction of prolyl 4-hydroxylase alpha (I) in cultured cells. |
| Journal | J Biol Chem |
| Abstract |
Accumulated evidence indicates that hypoxia activates collagen synthesis in tissues. To explore the molecular mechanism of activation, we screened genes that are up-regulated or down-regulated by hypoxia. Fibroblasts isolated from fetal rat lung were cultured under hypoxia. Differential display technique showed that the mRNA level of prolyl 4-hydroxylase (PH) alpha(I), an active subunit that catalyzes the oxygen-dependent hydroxylation of proline residue in procollagen, increased 2-3-fold after an 8-h exposure to hypoxia. This elevated level was maintained over 40 h and returned to the basal level after reoxygenation. The transcription rate, protein level, and hydroxyproline content (an indicator of the prolyl hydroxylation) were all elevated by hypoxic culture. Analysis of the promotor region of PHalpha(I) gene indicated that a motif similar to hypoxia-responsive element (HRE) of hypoxia-inducible genes such as erythropoietin, was identified within a 120-base pair sequence upstream of the transcription start site. Luciferase reporter assay and mutational analysis showed that a site similar to the HRE in this motif is functionally essential to hypoxic response. Electrophoretic mobility shift assay revealed that hypoxia-inducible factor-1 was stimulated and bound to the PHalpha(I) HRE upon hypoxic challenge. Our results indicate that PHalpha(I), an essential enzyme for collagen synthesis, is a target gene for hypoxia-inducible factor-1. |
| Volume | 275(19) |
| Pages | 14139-46 |
| Published | 2000-5-12 |
| DOI | 10.1074/jbc.275.19.14139 |
| PII | S0021-9258(19)80579-3 |
| PMID | 10799490 |
| MeSH | Animals Base Sequence Catalysis Cell Hypoxia* Cell Line Cloning, Molecular DNA / metabolism DNA Primers DNA-Binding Proteins / physiology Enzyme Induction Humans Hydroxylation Hypoxia-Inducible Factor 1 Hypoxia-Inducible Factor 1, alpha Subunit Isoenzymes / biosynthesis* Isoenzymes / genetics Kinetics Molecular Sequence Data Nuclear Proteins / physiology Procollagen-Proline Dioxygenase / biosynthesis* Procollagen-Proline Dioxygenase / genetics RNA, Messenger / genetics Rats Transcription Factors* Transcription, Genetic Up-Regulation |
| IF | 4.238 |
| Times Cited | 132 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 10 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | WI-38 |