Hypoxia-induced lactate dehydrogenase A protects cells from apoptosis in endometriosis
| Autor: | Na Liu, Qianmeng Huang, Jinyan Zheng, Li-Bing Shi, Xiang Lin, Y Dai, Feng Zhou, Songying Zhang, Xiaoying Jin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
endometriosis
Adult Cancer Research Stromal cell Epithelial-Mesenchymal Transition Lactate dehydrogenase A Cell lactate dehydrogenase A Apoptosis Protective Agents Biochemistry Flow cytometry Endometrium Genetics medicine Humans Glycolysis Lactic Acid RNA Messenger education Molecular Biology hypoxia-inducible factor 1α Cell Proliferation education.field_of_study Oncogene medicine.diagnostic_test L-Lactate Dehydrogenase Chemistry hypoxia Epithelial Cells Articles Cell cycle glycolysis Molecular biology medicine.anatomical_structure Oncology Molecular Medicine Female Lactate Dehydrogenase 5 Stromal Cells Reactive Oxygen Species |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| Popis: | The pathological expression and function of lactate dehydrogenase A (LDHA), a key enzyme that converts pyruvate into lactic acid during glycolysis, remains unknown in endometriosis. In the present study, LDHA expression in tissue samples was determined by immunohistochemistry. To examine whether LDHA was induced by hypoxia, primary cultured endometrial stromal cells (ESCs) and glandular epithelial Ishikawa cells were exposed to 1% O2 (hypoxia) or 21% O2 (normoxia). Cellular functions were assessed by flow cytometry, Transwell and Cell Counting Kit‑8 assays in LDHA‑silenced ESCs and Ishikawa cells. Mitochondrial functions were evaluated using mitochondrial membrane potential JC‑1 staining, reactive oxygen species flow cytometric analysis and ATP detection. Additionally, lactic acid production was examined and western blotting was used to evaluate the expression levels of proteins associated with apoptosis, cell cycle and glycolysis, as well as regulatory proteins involved in epithelial‑mesenchymal transformation and glycolytic pathways. LDHA was localized to endometrial glandular cells and stromal cells. However, LDHA protein expression was higher in endometriotic lesions compared with that in normal and eutopic endometria. LDHA expression levels in ectopic glandular cells were higher during the proliferative stage compared with during the secretory stage. Hypoxia treatment of Ishikawa cells and ESCs markedly induced the mRNA and protein expression of LDHA. Silencing of LDHA expression in Ishikawa cells and THESC cells significantly promoted impaired mitochondrial function and apoptosis while inhibiting migration and glycolysis. However, it had no obvious effect on proliferation. In conclusion, the present study revealed that LDHA was highly expressed in endometriotic tissues, where it may serve a notable role in the occurrence and development of endometriosis. |
| Databáze: | OpenAIRE |
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