Cytochrome-c-oxidase and ATPsynthase content increases in the endometrium of the patients with adenomyosis

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Adenomyosis patients showed increased alpha-actinin1 and cytochrome-c-oxidase/ATPsynthase levels, but not their mRNA, suggesting protein synthesis regulation changes.

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This study examined protein and mRNA levels of actin-binding proteins, cytochrome c, and mitochondrial respiratory-chain components in endometrial biopsies from patients with adenomyosis versus controls, using Western blotting and quantitative RT-PCR. The authors found higher alpha-actinin1 protein and its mRNA in adenomyosis (+86% and +84%, respectively) while alpha-actinin4 and cytochrome c were unchanged; cytochrome-c-oxidase and ATPsynthase proteins were increased (+270% and +121%), but the mRNAs for these genes did not change, suggesting regulation at the protein level. A limitation is that the paper’s conclusions are based on cross-sectional molecular measurements without functional assays of ATP production or direct assessment of apoptosis activity in the biopsied tissue. This paper is centrally about adenomyosis — it focuses on increased cytochrome-c-oxidase and ATPsynthase protein content in the endometrium of adenomyosis patients.

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Abstract

BACKGROUND: Adenomyosis is characterized by overgrowth of endometrial glands and stroma in the myometrium and is associated with reduced apoptosis. One of the key participants in one of the pathways of apoptosis is cytochrome c, whose expression can be regulated by actin-binding proteins involved in the formation of structures that provide cell motility. The aim of the study was to determine the content of actin-binding proteins, cytochrome c, and terminal members of the mitochondrial respiratory chain in endometrial biopsies of patients with adenomyosis and the control group. METHODS AND RESULTS: The content of all studied proteins was determined by Western blotting, and the mRNA content of the corresponding genes was determined by quantitative RT-PCR. The relative content of alpha-actinin1 and mRNA of the gene encoding it in biopsy specimens from patients with adenomyosis was higher than in controls by 86 and 84% (p < 0.05), respectively. The relative content of alpha-actinin4 did not change, as did cytochrome c. The content of cytochrome-c-oxidase and ATPsynthase in the group with adenomyosis exceeded the control level by 270 and 121% (p < 0.05), respectively, but the relative content of mRNA of these genes did not change, which may indicate a change in regulation at the level of protein synthesis. CONCLUSION: The results may indicate a local increase in the synthesis of ATP in pathological endometrial cells, which indicates the possible effectiveness of local application of H+-ATP synthase inhibitors (for example, macrolide antibiotic) to reduce the severity of clinical symptoms of adenomyosis.
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Abstract

Background Adenomyosis is characterized by overgrowth of endometrial glands and stroma in the myometrium and is associated with reduced apoptosis. One of the key participants in one of the pathways of apoptosis is cytochrome c, whose expression can be regulated by actin-binding proteins involved in the formation of structures that provide cell motility. The aim of the study was to determine the content of actin-binding proteins, cytochrome c, and terminal members of the mitochondrial respiratory chain in endometrial biopsies of patients with adenomyosis and the control group.

Methods

and results The content of all studied proteins was determined by Western blotting, and the mRNA content of the corresponding genes was determined by quantitative RT-PCR. The relative content of alpha-actinin1 and mRNA of the gene encoding it in biopsy specimens from patients with adenomyosis was higher than in controls by 86 and 84% (p < 0.05), respectively. The relative content of alpha-actinin4 did not change, as did cytochrome c. The content of cytochrome-c-oxidase and ATPsynthase in the group with adenomyosis exceeded the control level by 270 and 121% (p < 0.05), respectively, but the relative content of mRNA of these genes did not change, which may indicate a change in regulation at the level of protein synthesis.

Conclusion

The results may indicate a local increase in the synthesis of ATP in pathological endometrial cells, which indicates the possible effectiveness of local application of H+-ATP synthase inhibitors (for example, macrolide antibiotic) to reduce the severity of clinical symptoms of adenomyosis. Data availability All data generated or analyzed during this study are included in this article and supplementary materials.

References

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Methodology - KAT, EYG, MAG, VVP and IVO. Software - EYG and IVO. Validation - KAT, VVP, VVB and IVO. Formal analysis - KAT, VVP and IVO. Investigation - KAT, EYG, MAG, VVP and IVO. Resources - VVB and IVO. Data curation - KAT and IVO. Writing - original draft preparation - KAT and IVO. Writing-reviewing and editing - KAT, VVB and IVO. Visualization - EYG and IVO. Supervision - IVO. Project administration - VVB and IVO. Funding acquisition - KAT, VVB and IVO. All authors read and approved the final version of the manuscript. Corresponding author Ethics declarations Ethics approval The experimental plan and all procedures were approved by the Biomedical Ethics Committee of the Institute of Biomedical Problems of the Russian Academy of Sciences (Department of Physiology of the Russian Bioethics Committee, National Commission of the Russian Federation for UNESCO, Permit No. 523/MSK/09/26/19) and complies with the Declaration of Helsinki. Consent to participate Written informed consent to participate in this study was obtained from all patients. Consent to publish The authors confirm that participants in the human study gave informed consent to the publication of the images included in Figure S1. Conflict of interest The authors declare no conflict of interest. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Electronic supplementary material Below is the link to the electronic supplementary material. Rights and permissions About this article Cite this article Toniyan, K.A., Gorbacheva, E.Y., Golubkova, M.A. et al. Cytochrome-c-oxidase and ATPsynthase content increases in the endometrium of the patients with adenomyosis. Mol Biol Rep 50, 3919–3925 (2023). https://doi.org/10.1007/s11033-023-08269-9 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s11033-023-08269-9

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Condition tags

endometriosisadenomyosis

MeSH descriptors

Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis

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