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Transmembrane prolyl 4-hydroxylase is a fourth prolyl 4-hydroxylase regulating EPO production and erythropoiesis.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Laitala, Anu Aro, Ellinoora Walkinshaw, Gail Mäki, Joni M. Rossi, Maarit Heikkilä, Minna M. Savolainen, Eeva-Riitta Arend, Michael R. Kivirikko, Kari I. Koivunen, Peppi Myllyharju, Johanna |
| Copyright Year | 2012 |
| Abstract | An endoplasmic reticulum transmembrane prolyl 4-hydroxylase (P4H-TM) is able to hydroxylate the α subunit of the hypoxia-inducible factor (HIF) in vitro and in cultured cells, but nothing is known about its roles in mammalian erythropoiesis. We studied such roles here by administering a HIF-P4H inhibitor, FG-4497, to P4h-tm(-/-) mice. This caused larger increases in serum Epo concentration and kidney but not liver Hif-1α and Hif-2α protein and Epo mRNA levels than in wild-type mice, while the liver Hepcidin mRNA level was lower in the P4h-tm(-/-) mice than in the wild-type. Similar, but not identical, differences were also seen between FG-4497-treated Hif-p4h-2 hypomorphic (Hif-p4h-2(gt/gt)) and Hif-p4h-3(-/-) mice versus wild-type mice. FG-4497 administration increased hemoglobin and hematocrit values similarly in the P4h-tm(-/-) and wild-type mice, but caused higher increases in both values in the Hif-p4h-2(gt/gt) mice and in hematocrit value in the Hif-p4h-3(-/-) mice than in the wild-type. Hif-p4h-2(gt/gt)/P4h-tm(-/-) double gene-modified mice nevertheless had increased hemoglobin and hematocrit values without any FG-4497 administration, although no such abnormalities were seen in the Hif-p4h-2(gt/gt) or P4h-tm(-/-) mice. Our data thus indicate that P4H-TM plays a role in the regulation of EPO production, hepcidin expression, and erythropoiesis. |
| Starting Page | 94 |
| Ending Page | 100 |
| Page Count | 7 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.bloodjournal.org/content/bloodjournal/early/2012/09/05/blood-2012-07-441824.full.pdf?sso-checked=true |
| PubMed reference number | 22955912v1 |
| Alternate Webpage(s) | https://doi.org/10.1182/blood-2012-07-441824 |
| DOI | 10.1182/blood-2012-07-441824 |
| Journal | Blood |
| Volume Number | 120 |
| Issue Number | 16 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Administration procedure Congenital Abnormality Erythropoiesis F Factor HAMP gene Hypoxia Inducible Factor Family Hypoxia-Inducible Factor-Proline Dioxygenases Large Mammals Procollagen-Proline Dioxygenase Renal Tissue hepcidin |
| Content Type | Text |
| Resource Type | Article |
