Calpain Regulates Reactive Oxygen Species Production during Capacitation through the Activation of NOX2 and NOX4.

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Title: Calpain Regulates Reactive Oxygen Species Production during Capacitation through the Activation of NOX2 and NOX4.
Authors: Ortiz-García, César I.1 (AUTHOR), Salgado-Lucio, Monica L.1,2 (AUTHOR), Roa-Espitia, Ana L.1 (AUTHOR), Muñoz-Sánchez, Aidé A.1 (AUTHOR), Cordero-Martínez, Joaquín3 (AUTHOR), Hernández-González, Enrique O.1 (AUTHOR) enrique.hernandez@cinvestav.mx
Source: International Journal of Molecular Sciences. Feb2023, Vol. 24 Issue 4, p3980. 18p.
Subject Terms: *REACTIVE oxygen species, *CALPAIN, *ACROSOME reaction, *GUINEA pigs, *SPERMATOZOA, *OXIDASES
Abstract: 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 Ca2+ 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 Ca2+-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. [ABSTRACT FROM AUTHOR]
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  Label: Title
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  Data: Calpain Regulates Reactive Oxygen Species Production during Capacitation through the Activation of NOX2 and NOX4.
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  Data: <searchLink fieldCode="AR" term="%22Ortiz-García%2C+César+I%2E%22">Ortiz-García, César I.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Salgado-Lucio%2C+Monica+L%2E%22">Salgado-Lucio, Monica L.</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Roa-Espitia%2C+Ana+L%2E%22">Roa-Espitia, Ana L.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Muñoz-Sánchez%2C+Aidé+A%2E%22">Muñoz-Sánchez, Aidé A.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cordero-Martínez%2C+Joaquín%22">Cordero-Martínez, Joaquín</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hernández-González%2C+Enrique+O%2E%22">Hernández-González, Enrique O.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> enrique.hernandez@cinvestav.mx</i>
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  Data: <searchLink fieldCode="JN" term="%22International+Journal+of+Molecular+Sciences%22">International Journal of Molecular Sciences</searchLink>. Feb2023, Vol. 24 Issue 4, p3980. 18p.
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  Data: *<searchLink fieldCode="DE" term="%22REACTIVE+oxygen+species%22">REACTIVE oxygen species</searchLink><br />*<searchLink fieldCode="DE" term="%22CALPAIN%22">CALPAIN</searchLink><br />*<searchLink fieldCode="DE" term="%22ACROSOME+reaction%22">ACROSOME reaction</searchLink><br />*<searchLink fieldCode="DE" term="%22GUINEA+pigs%22">GUINEA pigs</searchLink><br />*<searchLink fieldCode="DE" term="%22SPERMATOZOA%22">SPERMATOZOA</searchLink><br />*<searchLink fieldCode="DE" term="%22OXIDASES%22">OXIDASES</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: 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 Ca2+ 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 Ca2+-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. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of International Journal of Molecular Sciences is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.3390/ijms24043980
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        Text: English
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        PageCount: 18
        StartPage: 3980
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      – SubjectFull: REACTIVE oxygen species
        Type: general
      – SubjectFull: CALPAIN
        Type: general
      – SubjectFull: ACROSOME reaction
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      – SubjectFull: GUINEA pigs
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      – SubjectFull: SPERMATOZOA
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      – SubjectFull: OXIDASES
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      – TitleFull: Calpain Regulates Reactive Oxygen Species Production during Capacitation through the Activation of NOX2 and NOX4.
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              Text: Feb2023
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              Y: 2023
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