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Redox regulation of mammalian sperm capacitation.

O'Flaherty C - Asian J. Androl. (2015 Jul-Aug)

Bottom Line: Both, oxidation of thiols forming disulfide bridges and the increase on thiol content are necessary to regulate different sperm proteins associated with capacitation.Reducing equivalents such as NADH and NADPH are necessary to support capacitation in many species including humans.The dysregulation of PRDXs and of enzymes needed for their reactivation such as thioredoxin/thioredoxin reductase system and glutathione-S-transferases impairs sperm motility, capacitation, and promotes DNA damage in spermatozoa leading to male infertility.

View Article: PubMed Central - PubMed

Affiliation: Urology Research Laboratory, Surgery Department (Urology Division), Faculty of Medicine, McGill University; The Research Institute, McGill University Health Centre, Montréal, Québec, Canada.

ABSTRACT
Capacitation is a series of morphological and metabolic changes necessary for the spermatozoon to achieve fertilizing ability. One of the earlier happenings during mammalian sperm capacitation is the production of reactive oxygen species (ROS) that will trigger and regulate a series of events including protein phosphorylation, in a time-dependent fashion. The identity of the sperm oxidase responsible for the production of ROS involved in capacitation is still elusive, and several candidates are discussed in this review. Interestingly, ROS-induced ROS formation has been described during human sperm capacitation. Redox signaling during capacitation is associated with changes in thiol groups of proteins located on the plasma membrane and subcellular compartments of the spermatozoon. Both, oxidation of thiols forming disulfide bridges and the increase on thiol content are necessary to regulate different sperm proteins associated with capacitation. Reducing equivalents such as NADH and NADPH are necessary to support capacitation in many species including humans. Lactate dehydrogenase, glucose-6-phospohate dehydrogenase, and isocitrate dehydrogenase are responsible in supplying NAD (P) H for sperm capacitation. Peroxiredoxins (PRDXs) are newly described enzymes with antioxidant properties that can protect mammalian spermatozoa; however, they are also candidates for assuring the regulation of redox signaling required for sperm capacitation. The dysregulation of PRDXs and of enzymes needed for their reactivation such as thioredoxin/thioredoxin reductase system and glutathione-S-transferases impairs sperm motility, capacitation, and promotes DNA damage in spermatozoa leading to male infertility.

No MeSH data available.


Related in: MedlinePlus

Role of lactate dehydrogenase as a supplier of NADH for bull sperm capacitation. Cytosolic and mitochondrial LDHC4 are important to supply NADH for the sperm oxidase that produces extracellular O2•– for bull sperm capacitation. Lactate is converted by the LDH-C4cyt into pyruvate and NADH that will be used as oxidases for capacitation. The pyruvate will enter into the mitochondrion to be converted into acetyl-CoA and enter into the Krebs cycle. Then, reducing equivalents will be transferred to the respiratory chain to produce ATP that will be used for energy purposes and to provide phosphate groups for a series of phosphorylation events. AC: adenylyl cyclase; PLC: phospholipase C; PKA: protein kinase A; PKC: protein kinase C; PTK: protein tyrosine kinase; O2•–: superoxide anion; LDH-C4cyt: cytosolic lactate dehydrogenase-C4.
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Figure 2: Role of lactate dehydrogenase as a supplier of NADH for bull sperm capacitation. Cytosolic and mitochondrial LDHC4 are important to supply NADH for the sperm oxidase that produces extracellular O2•– for bull sperm capacitation. Lactate is converted by the LDH-C4cyt into pyruvate and NADH that will be used as oxidases for capacitation. The pyruvate will enter into the mitochondrion to be converted into acetyl-CoA and enter into the Krebs cycle. Then, reducing equivalents will be transferred to the respiratory chain to produce ATP that will be used for energy purposes and to provide phosphate groups for a series of phosphorylation events. AC: adenylyl cyclase; PLC: phospholipase C; PKA: protein kinase A; PKC: protein kinase C; PTK: protein tyrosine kinase; O2•–: superoxide anion; LDH-C4cyt: cytosolic lactate dehydrogenase-C4.

Mentions: Spermatozoa from the bull (and other species) utilize pyruvate and lactate (generated by LDH-C4) as oxidative substrates for mitochondrial respiration69 and capacitation65 (Figure 2). The cytosolic isoform of LDH-C4 converts lactate into pyruvate and NADH. Then, pyruvate can enter into the mitochondrial to be converted into acetyl-CoA by pyruvate dehydrogenase and enters into the Krebs cycle to generate reducing equivalents that will be used in the respiratory chain to generate ATP. This ATP will be used for energy purposes and to provide phosphate groups to support the series of phosphorylation events required during sperm capacitation.226570 The pyruvate not used for energy purposes could be converted into lactate by mitochondrial LDH-C4 and will diffuse to the cytosol to re-feed the production of O2•– by the oxidase65 (Figure 2).


Redox regulation of mammalian sperm capacitation.

O'Flaherty C - Asian J. Androl. (2015 Jul-Aug)

Role of lactate dehydrogenase as a supplier of NADH for bull sperm capacitation. Cytosolic and mitochondrial LDHC4 are important to supply NADH for the sperm oxidase that produces extracellular O2•– for bull sperm capacitation. Lactate is converted by the LDH-C4cyt into pyruvate and NADH that will be used as oxidases for capacitation. The pyruvate will enter into the mitochondrion to be converted into acetyl-CoA and enter into the Krebs cycle. Then, reducing equivalents will be transferred to the respiratory chain to produce ATP that will be used for energy purposes and to provide phosphate groups for a series of phosphorylation events. AC: adenylyl cyclase; PLC: phospholipase C; PKA: protein kinase A; PKC: protein kinase C; PTK: protein tyrosine kinase; O2•–: superoxide anion; LDH-C4cyt: cytosolic lactate dehydrogenase-C4.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492048&req=5

Figure 2: Role of lactate dehydrogenase as a supplier of NADH for bull sperm capacitation. Cytosolic and mitochondrial LDHC4 are important to supply NADH for the sperm oxidase that produces extracellular O2•– for bull sperm capacitation. Lactate is converted by the LDH-C4cyt into pyruvate and NADH that will be used as oxidases for capacitation. The pyruvate will enter into the mitochondrion to be converted into acetyl-CoA and enter into the Krebs cycle. Then, reducing equivalents will be transferred to the respiratory chain to produce ATP that will be used for energy purposes and to provide phosphate groups for a series of phosphorylation events. AC: adenylyl cyclase; PLC: phospholipase C; PKA: protein kinase A; PKC: protein kinase C; PTK: protein tyrosine kinase; O2•–: superoxide anion; LDH-C4cyt: cytosolic lactate dehydrogenase-C4.
Mentions: Spermatozoa from the bull (and other species) utilize pyruvate and lactate (generated by LDH-C4) as oxidative substrates for mitochondrial respiration69 and capacitation65 (Figure 2). The cytosolic isoform of LDH-C4 converts lactate into pyruvate and NADH. Then, pyruvate can enter into the mitochondrial to be converted into acetyl-CoA by pyruvate dehydrogenase and enters into the Krebs cycle to generate reducing equivalents that will be used in the respiratory chain to generate ATP. This ATP will be used for energy purposes and to provide phosphate groups to support the series of phosphorylation events required during sperm capacitation.226570 The pyruvate not used for energy purposes could be converted into lactate by mitochondrial LDH-C4 and will diffuse to the cytosol to re-feed the production of O2•– by the oxidase65 (Figure 2).

Bottom Line: Both, oxidation of thiols forming disulfide bridges and the increase on thiol content are necessary to regulate different sperm proteins associated with capacitation.Reducing equivalents such as NADH and NADPH are necessary to support capacitation in many species including humans.The dysregulation of PRDXs and of enzymes needed for their reactivation such as thioredoxin/thioredoxin reductase system and glutathione-S-transferases impairs sperm motility, capacitation, and promotes DNA damage in spermatozoa leading to male infertility.

View Article: PubMed Central - PubMed

Affiliation: Urology Research Laboratory, Surgery Department (Urology Division), Faculty of Medicine, McGill University; The Research Institute, McGill University Health Centre, Montréal, Québec, Canada.

ABSTRACT
Capacitation is a series of morphological and metabolic changes necessary for the spermatozoon to achieve fertilizing ability. One of the earlier happenings during mammalian sperm capacitation is the production of reactive oxygen species (ROS) that will trigger and regulate a series of events including protein phosphorylation, in a time-dependent fashion. The identity of the sperm oxidase responsible for the production of ROS involved in capacitation is still elusive, and several candidates are discussed in this review. Interestingly, ROS-induced ROS formation has been described during human sperm capacitation. Redox signaling during capacitation is associated with changes in thiol groups of proteins located on the plasma membrane and subcellular compartments of the spermatozoon. Both, oxidation of thiols forming disulfide bridges and the increase on thiol content are necessary to regulate different sperm proteins associated with capacitation. Reducing equivalents such as NADH and NADPH are necessary to support capacitation in many species including humans. Lactate dehydrogenase, glucose-6-phospohate dehydrogenase, and isocitrate dehydrogenase are responsible in supplying NAD (P) H for sperm capacitation. Peroxiredoxins (PRDXs) are newly described enzymes with antioxidant properties that can protect mammalian spermatozoa; however, they are also candidates for assuring the regulation of redox signaling required for sperm capacitation. The dysregulation of PRDXs and of enzymes needed for their reactivation such as thioredoxin/thioredoxin reductase system and glutathione-S-transferases impairs sperm motility, capacitation, and promotes DNA damage in spermatozoa leading to male infertility.

No MeSH data available.


Related in: MedlinePlus