Calpain Regulates Reactive Oxygen Species Production during Capacitation through the Activation of NOX2 and NOX4
Capacitation is a series of physiological, biochemical, and metabolic changes experienced by mammalian spermatozoa. These changes enable them to fertilize eggs. The capacitation prepares the spermatozoa to undergo the acrosomal reaction and hyperactivated motility. Several mechanisms that regulate c...
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/4/3980 |
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| author | César I. Ortiz-García Monica L. Salgado-Lucio Ana L. Roa-Espitia Aidé A. Muñoz-Sánchez Joaquín Cordero-Martínez Enrique O. Hernández-González |
| author_facet | César I. Ortiz-García Monica L. Salgado-Lucio Ana L. Roa-Espitia Aidé A. Muñoz-Sánchez Joaquín Cordero-Martínez Enrique O. Hernández-González |
| author_sort | César I. Ortiz-García |
| collection | DOAJ |
| description | Capacitation is a series of physiological, biochemical, and metabolic changes experienced by mammalian spermatozoa. These changes enable them to fertilize eggs. The capacitation prepares the spermatozoa to undergo the acrosomal reaction and hyperactivated motility. Several mechanisms that regulate capacitation are known, although they have not been fully disclosed; among them, reactive oxygen species (ROS) play an essential role in the normal development of capacitation. NADPH oxidases (NOXs) are a family of enzymes responsible for ROS production. Although their presence in mammalian sperm is known, little is known about their participation in sperm physiology. This work aimed to identify the NOXs related to the production of ROS in guinea pig and mouse spermatozoa and define their participation in capacitation, acrosomal reaction, and motility. Additionally, a mechanism for NOXs’ activation during capacitation was established. The results show that guinea pig and mouse spermatozoa express NOX2 and NOX4, which initiate ROS production during capacitation. NOXs inhibition by VAS2870 led to an early increase in the capacitation and intracellular concentration of Ca<sup>2+</sup> in such a way that the spermatozoa also presented an early acrosome reaction. In addition, the inhibition of NOX2 and NOX4 reduced progressive motility and hyperactive motility. NOX2 and NOX4 were found to interact with each other prior to capacitation. This interaction was interrupted during capacitation and correlated with the increase in ROS. Interestingly, the association between NOX2-NOX4 and their activation depends on calpain activation, since the inhibition of this Ca<sup>2+</sup>-dependent protease prevents NOX2-NOX4 from dissociating and ROS production. The results indicate that NOX2 and NOX4 could be the most important ROS producers during guinea pig and mouse sperm capacitation and that their activation depends on calpain. |
| first_indexed | 2024-03-11T08:41:44Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T08:41:44Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4d5afe82fb7045d9b27b07927838d80b2023-11-16T21:07:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244398010.3390/ijms24043980Calpain Regulates Reactive Oxygen Species Production during Capacitation through the Activation of NOX2 and NOX4César I. Ortiz-García0Monica L. Salgado-Lucio1Ana L. Roa-Espitia2Aidé A. Muñoz-Sánchez3Joaquín Cordero-Martínez4Enrique O. Hernández-González5Department of Cell Biology, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, San Pedro Zacatenco, Del. Gustavo A. Madero, México City 07360, MexicoDepartment of Cell Biology, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, San Pedro Zacatenco, Del. Gustavo A. Madero, México City 07360, MexicoDepartment of Cell Biology, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, San Pedro Zacatenco, Del. Gustavo A. Madero, México City 07360, MexicoDepartment of Cell Biology, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, San Pedro Zacatenco, Del. Gustavo A. Madero, México City 07360, MexicoDepartment of Biochemistry, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación Manuel Carpio y Plan de Ayala s/n Col, Santo Tomás, Del. Miguel Hidalgo, México City 11340, MexicoDepartment of Cell Biology, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, San Pedro Zacatenco, Del. Gustavo A. Madero, México City 07360, MexicoCapacitation is a series of physiological, biochemical, and metabolic changes experienced by mammalian spermatozoa. These changes enable them to fertilize eggs. The capacitation prepares the spermatozoa to undergo the acrosomal reaction and hyperactivated motility. Several mechanisms that regulate capacitation are known, although they have not been fully disclosed; among them, reactive oxygen species (ROS) play an essential role in the normal development of capacitation. NADPH oxidases (NOXs) are a family of enzymes responsible for ROS production. Although their presence in mammalian sperm is known, little is known about their participation in sperm physiology. This work aimed to identify the NOXs related to the production of ROS in guinea pig and mouse spermatozoa and define their participation in capacitation, acrosomal reaction, and motility. Additionally, a mechanism for NOXs’ activation during capacitation was established. The results show that guinea pig and mouse spermatozoa express NOX2 and NOX4, which initiate ROS production during capacitation. NOXs inhibition by VAS2870 led to an early increase in the capacitation and intracellular concentration of Ca<sup>2+</sup> in such a way that the spermatozoa also presented an early acrosome reaction. In addition, the inhibition of NOX2 and NOX4 reduced progressive motility and hyperactive motility. NOX2 and NOX4 were found to interact with each other prior to capacitation. This interaction was interrupted during capacitation and correlated with the increase in ROS. Interestingly, the association between NOX2-NOX4 and their activation depends on calpain activation, since the inhibition of this Ca<sup>2+</sup>-dependent protease prevents NOX2-NOX4 from dissociating and ROS production. The results indicate that NOX2 and NOX4 could be the most important ROS producers during guinea pig and mouse sperm capacitation and that their activation depends on calpain.https://www.mdpi.com/1422-0067/24/4/3980NADPH oxidasesROS productioncapacitationacrosome reactionmobilitycalcium |
| spellingShingle | César I. Ortiz-García Monica L. Salgado-Lucio Ana L. Roa-Espitia Aidé A. Muñoz-Sánchez Joaquín Cordero-Martínez Enrique O. Hernández-González Calpain Regulates Reactive Oxygen Species Production during Capacitation through the Activation of NOX2 and NOX4 International Journal of Molecular Sciences NADPH oxidases ROS production capacitation acrosome reaction mobility calcium |
| title | Calpain Regulates Reactive Oxygen Species Production during Capacitation through the Activation of NOX2 and NOX4 |
| title_full | Calpain Regulates Reactive Oxygen Species Production during Capacitation through the Activation of NOX2 and NOX4 |
| title_fullStr | Calpain Regulates Reactive Oxygen Species Production during Capacitation through the Activation of NOX2 and NOX4 |
| title_full_unstemmed | Calpain Regulates Reactive Oxygen Species Production during Capacitation through the Activation of NOX2 and NOX4 |
| title_short | Calpain Regulates Reactive Oxygen Species Production during Capacitation through the Activation of NOX2 and NOX4 |
| title_sort | calpain regulates reactive oxygen species production during capacitation through the activation of nox2 and nox4 |
| topic | NADPH oxidases ROS production capacitation acrosome reaction mobility calcium |
| url | https://www.mdpi.com/1422-0067/24/4/3980 |
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