Endogenous H2S production deficiencies lead to impaired renal erythropoietin production
| Autor: | Peng Shao, Martin Feelisch, Rui Wang, Jennifer Leigh, Matthias Bachtler, Alp Sener, Masoud Akbari, Zhongming Qian, Bernadette O. Fernandez, Harry van Goor, Andreas Pasch, Smriti Juriasingani, Ian Lobb, Manujendra N. Saha |
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| Přispěvatelé: | Groningen Institute for Organ Transplantation (GIOT), Groningen Kidney Center (GKC) |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Anemia Urology Urinary system urologic and male genital diseases 03 medical and health sciences Internal medicine medicine Original Research biology business.industry Hypoxia (medical) equipment and supplies medicine.disease Cystathionine beta synthase 030104 developmental biology Endocrinology Oncology Erythropoietin Knockout mouse biology.protein Hemoglobin medicine.symptom business Kidney disease medicine.drug |
| Zdroj: | Canadian Urological Association journal = Journal de l'Association des urologues du Canada, 13(7), E210-E219. CANADIAN UROLOGICAL ASSOCIATION |
| ISSN: | 1920-1214 1911-6470 |
| DOI: | 10.5489/cuaj.5658 |
| Popis: | INTRODUCTION: Patients suffering from chronic kidney disease (CKD) experience a number of associated comorbidities, including anemia. Relative deficiency in renal erythropoietin (EPO) production is thought to be a primary cause of anemia. Interestingly, CKD patients display low levels of hydrogen sulfide (H2S), an endogenously derived renal oxygen sensor. Previous in vitro experiments have revealed that H2S-deficient renal cell lines produce less EPO than wild-type renal cell lines during hypoxia.METHODS: We postulated that H2S might be a primary mediator of EPO synthesis during hypoxia, which was tested using an in vivo murine model of whole-body hypoxia and in clinical samples obtained from CKD patients.RESULTS: Following a 72-hour period of hypoxia (11% O2), partial H2S knockout mice (lacking the H2S biosynthetic enzyme cystathionine γ-lyase [CSE]) displayed lower levels of hemoglobin, EPO and cystathionine-β-synthase (CBS) (another H2S biosynthetic enzyme) compared to wild-type mice, all of which was rescued by exogenous H2S supplementation. We also found that anemic CKD patients requiring exogenous EPO exhibited lower urinary thiosulfate levels compared to non-anemic CKD patients of similar CKD classification.CONCLUSIONS: Together, our results confirm an interplay between the actions of H2S during hypoxia and EPO production. |
| Databáze: | OpenAIRE |
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