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. 2023 Jan 20;12(2):239. doi: 10.3390/antiox12020239

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© 2023 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Soluble Klotho-mediated antioxidant mechanisms. Membrane Klotho can be cleaved by membrane-anchored secretases ADAM10/17, which release the extracellular domain into the extracellular space. Soluble Klotho decreases oxidative stress via the inhibition of insulin/IGF-1/PI3K/Akt/FoxO pathway, promoting the expression of superoxide dismutase (SOD2) and catalase (CAT). Similarly, soluble Klotho also reduces oxidative stress through the activation of the cellular protective Nrf2 pathway, which promotes the transcription of genes related to antioxidant defense, such as hemeoxygenase-1 (HO-1), SOD2, CAT, and glutathione peroxidase (GPX), among others.