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Periodicum biologorum, Vol. 125 No. 3-4, 2023.

Original scientific paper

https://doi.org/10.18054/pb.v125i3-4.30257

Sex-Related Differences in Oxidant and Antioxidant Profiles of Murine Kidney and Brain: A Focus on Sirt3-Mediated Regulation

Robert Belužić ; Laboratory for Metabolism and Aging, Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia
Marta Kaloper ; Department of Biology, Faculty of Science, University of Zagreb, Croatia
Marija Pinterić orcid id orcid.org/0000-0003-1049-0237 ; Laboratory for Metabolism and Aging, Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia
Iva I. Podgorski orcid id orcid.org/0000-0002-9423-9711 ; Laboratory for Metabolism and Aging, Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia
Ena Šimunić orcid id orcid.org/0000-0003-0011-1985 ; Laboratory for Metabolism and Aging, Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia
Marijana Popović Hadžija orcid id orcid.org/0000-0001-6522-3721 ; Laboratory for Metabolism and Aging, Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia
Tihomir Balog ; Laboratory for Metabolism and Aging, Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia
Sandra Sobočanec orcid id orcid.org/0000-0001-8915-6009 ; Laboratory for Metabolism and Aging, Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia

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Abstract

Background: Sirt3 is a mitochondrial deacetylase with an important role in maintainance of cellular redox and metabolic homeostasis and mitochondrial function. As growing evidence support the existence of sex-specific responses to metabolic and oxidative stress, we aimed to investigate sex- and organ-specific effects of Sirt3 loss.
Materials and methods: Expression of Sirt3, PGC-1a, CuZnSOD, MnSOD and Cat proteins in kidneys and brains of Sirt3-wild type (Sirt3 WT) and Sirt3-knockout (Sirt3 KO) mice was assessed by Western blotting. Protein carbonylation and lipid peroxidation levels were measured using ELISA and fluorometric assays, respectively. SOD and Cat activities were determined using standard enzymatic assays.
Results: Significant sex- and organ- specific differences in response to Sirt3 loss were detected. Sirt3 knockout affected kidneys more than brain tissue, with females showing lower levels PC and LPO. In kidneys, female KO showed higher MnSOD, but lower CuZnSOD and Cat activity compared to males. In brains, WT females show higher activities of these enzymes than males, suggesting a sex-specific protection mechanism, but female KO brains show a larger decrease in these parameters.
Conclusion: Our study provides comprehensive insights into the complex interplay of Sirt3, oxidative stress, and antioxidant defenses in murine kidney and brain. The observed differences between the two organs and the impact of sex highlight the need for studying Sirt3 function in diverse physiological contexts. The tissue-specific responses and sex-related variations underscore the importance of considering these factors in the development of therapeutic strategies targeting mitochondrial function and redox homeostasis.

Keywords

sirtuin 3; sex; mouse; oxidative stress; antioxidant enzymes; kidney; brain

Hrčak ID:

318124

URI

https://hrcak.srce.hr/318124

Publication date:

31.5.2024.

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