A potential role of Sirtuin3 and its target enzyme activities in patients with ovarian endometrioma

Abstract

Objective

Sirtuin3 (SIRT3) is a NAD⁺-dependent major mitochondrial deacetylase. In this study, we aimed to investigate SIRT3 levels and their target enzyme activities, including glutamate dehydrogenase (GDH), succinate dehydrogenase (SDH), and manganese superoxide dismutase (MnSOD), also to determine the antioxidant capacity and oxidative stress in tissue, mitochondria and serum samples in ovarian endometrioma patients.

Methods

We collected serum and endometrioma tissue samples from 30 patients. In the control group, we collected serum and eutopic endometrial tissue samples from 26 women without endometriosis.

Results

SIRT3 levels were significantly decreased in endometrioma tissue samples compared to the control group. There was no statistically significant difference in SIRT3 levels between patient and control serum samples. Furthermore, there was a decrease in GDH and SDH enzyme activities in both endometrioma tissue homogenate and mitochondria. MnSOD activity was decreased in tissue homogenate but increased in mitochondria and there was no difference in serum. While total SOD activity was decreased, CuZnSOD activity was increased in both tissue and serum samples. Besides these, total antioxidant capacity and advanced oxidation protein products (AOPP) levels were decreased in endometrioma tissue and mitochondria, but there was no difference in serum.

Conclusions

Our results suggested that decreased levels of SIRT3 in endometrioma may be an important factor in the weakening of mitochondrial energy metabolism and antioxidant defense in endometriosis. We think that SIRT3 deficiency may be an important factor underlying the pathogenesis of endometriosis. More detailed studies are needed to reveal the relationship between SIRT3 and metabolism and oxidative stress in ovarian endometrioma.

卵巢子宫内膜异位症患者Sirtuin3的潜在作用及其目标酶活性 摘要

目的：沉默调节蛋白sirtuin3（SIRT3）是一种烟酰胺腺嘌呤二核苷酸（NAD+）依赖的去乙酰化酶, 主要位于线粒体中。SIRT3的目标酶包括谷氨酸脱氢酶（GDH）、琥珀酸脱氢酶（SDH）以及锰超氧化物歧化酶（MnSOD）。在本研究中, 我们检测了卵巢子宫内膜异位症患者病灶组织、线粒体和血清样本中的SIRT3水平及其目标酶活性, 并测定了其抗氧化能力和氧化应激状态。

方法：我们收集了30例卵巢子宫内膜异位症患者的血清及其异位病灶的标本。在对照组中, 我们收集了26例非子宫内膜异位症女性的血清及其子宫内膜标本。

结果： SIRT3在子宫内膜异位灶标本中的水平, 较对照组显著降低。SIRT3在血清标本中的水平, 患病组与对照组无显著统计学差异。GDH和SDH的酶活性在子宫内膜异位灶的组织匀浆和线粒体中呈现降低。MnSOD活性在异位病灶的组织匀浆中降低, 在线粒体中升高, 在血清中无显著变化。在患者的异位病灶组织及血清中, 虽然SOD的总活性降低了, 但铜锌SOD的活性却均升高。此外, 总抗氧化能力与晚期氧化蛋白产物（AOPP）在异位病灶组织及线粒体中呈现降低, 但在血清中并无显著变化。

结论：我们的研究结果显示, SIRT3在子宫内膜异位症中的下调可能是异位病灶线粒体能量代谢和抗氧化防御减弱的重要因素。我们认为, SIRT3的缺乏可能是子宫内膜异位症发病机制中的一个重要因素。在卵巢子宫内膜异位症中, SIRT3与代谢及氧化应激的关系, 尚需进一步详细的研究。

Keywords:

• Ovarian endometrioma
• mitochondria
• Sirtuin3
• energy metabolism
• oxidative stress

Author contribution

İK: Project development, data collection, data analysis, manuscript writing. ASA, AG: Project development, data collection, manuscript editing. EU: Project development, data analysis, manuscript writing. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethical approval

Ethical approval was obtained from Istanbul University-Cerrahpaşa, Cerrahpaşa Medical Faculty Clinical Research Ethics Committee (211905).

Consent to participate

This study was conducted in accordance to the Declaration of Helsinki and informed consent was obtained from all individual participants included in the study.

Data availability statement

All data generated or analyzed during this study are shown in this article.

Additional information

Funding

This work was supported by the Research Fund of Istanbul University-Cerrahpaşa [Project No. 22761]