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Hypoxia‑induced lactate dehydrogenase A protects cells from apoptosis in endometriosis

  • Authors:
    • Jinyan Zheng
    • Yongdong Dai
    • Xiang Lin
    • Qianmeng Huang
    • Libing Shi
    • Xiaoying Jin
    • Na Liu
    • Feng Zhou
    • Songying Zhang
  • View Affiliations / Copyright

    Affiliations: Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, P.R. China
    Copyright: © Zheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 637
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    Published online on: July 6, 2021
       https://doi.org/10.3892/mmr.2021.12276
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Abstract

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.
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Copy and paste a formatted citation
Spandidos Publications style
Zheng J, Dai Y, Lin X, Huang Q, Shi L, Jin X, Liu N, Zhou F and Zhang S: Hypoxia‑induced lactate dehydrogenase A protects cells from apoptosis in endometriosis. Mol Med Rep 24: 637, 2021.
APA
Zheng, J., Dai, Y., Lin, X., Huang, Q., Shi, L., Jin, X. ... Zhang, S. (2021). Hypoxia‑induced lactate dehydrogenase A protects cells from apoptosis in endometriosis. Molecular Medicine Reports, 24, 637. https://doi.org/10.3892/mmr.2021.12276
MLA
Zheng, J., Dai, Y., Lin, X., Huang, Q., Shi, L., Jin, X., Liu, N., Zhou, F., Zhang, S."Hypoxia‑induced lactate dehydrogenase A protects cells from apoptosis in endometriosis". Molecular Medicine Reports 24.3 (2021): 637.
Chicago
Zheng, J., Dai, Y., Lin, X., Huang, Q., Shi, L., Jin, X., Liu, N., Zhou, F., Zhang, S."Hypoxia‑induced lactate dehydrogenase A protects cells from apoptosis in endometriosis". Molecular Medicine Reports 24, no. 3 (2021): 637. https://doi.org/10.3892/mmr.2021.12276
Copy and paste a formatted citation
x
Spandidos Publications style
Zheng J, Dai Y, Lin X, Huang Q, Shi L, Jin X, Liu N, Zhou F and Zhang S: Hypoxia‑induced lactate dehydrogenase A protects cells from apoptosis in endometriosis. Mol Med Rep 24: 637, 2021.
APA
Zheng, J., Dai, Y., Lin, X., Huang, Q., Shi, L., Jin, X. ... Zhang, S. (2021). Hypoxia‑induced lactate dehydrogenase A protects cells from apoptosis in endometriosis. Molecular Medicine Reports, 24, 637. https://doi.org/10.3892/mmr.2021.12276
MLA
Zheng, J., Dai, Y., Lin, X., Huang, Q., Shi, L., Jin, X., Liu, N., Zhou, F., Zhang, S."Hypoxia‑induced lactate dehydrogenase A protects cells from apoptosis in endometriosis". Molecular Medicine Reports 24.3 (2021): 637.
Chicago
Zheng, J., Dai, Y., Lin, X., Huang, Q., Shi, L., Jin, X., Liu, N., Zhou, F., Zhang, S."Hypoxia‑induced lactate dehydrogenase A protects cells from apoptosis in endometriosis". Molecular Medicine Reports 24, no. 3 (2021): 637. https://doi.org/10.3892/mmr.2021.12276
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