Regulation of Phosphorylation of Glycogen Synthase Kinase 3α and the Correlation with Sperm Motility in Human
Copyright © 2024 Korean Society for Sexual Medicine and Andrology..
PURPOSE: To unravel the mechanism regulating the phosphorylation of glycogen synthase kinase 3 (GSK3) and the correlation between the inhibitory phosphorylation of GSK3α and sperm motility in human.
MATERIALS AND METHODS: The phosphorylation and priming phosphorylated substrate-specific kinase activity of GSK3 were examined in human spermatozoa with various motility conditions.
RESULTS: In human spermatozoa, GSK3α/β was localized in the head, midpiece, and principal piece of tail and p-GSK3α(Ser21) was enriched in the midpiece. The ratio of p-GSK3α(Ser21)/GSK3α was positively coupled with normal sperm motility criteria of World Health Organization. In high-motility spermatozoa, p-GSK3α(Ser21) phosphotyrosine (p-Tyr) proteins but p-GSK3α(Tyr279) markedly increased together with decreased kinase activity of GSK3 after incubation in Ca2+ containing medium. In high-motility spermatozoa, p-GSK3α(Ser21) levels were negatively coupled with kinase activity of GSK3, and which was deregulated in low-motility spermatozoa. In high-motility spermatozoa, 6-bromo-indirubin-3'-oxime, an inhibitor of kinase activity of GSK3 increased p-GSK3α(Ser21) and p-Tyr proteins. p-GSK3α(Ser21) and p-Tyr protein levels were decreased by inhibition of PKA and Akt. Calyculin A, a protein phosphatase-1/2A inhibitor, markedly increased the p-GSK3α(Ser21) and p-Tyr proteins, and significantly increased the motility of low-motility human spermatozoa.
CONCLUSIONS: Down regulation of kinase activity of GSK3α by inhibitory phosphorylation was positively coupled with human sperm motility, and which was regulated by Ca2+, PKA, Akt, and PP1. Small-molecule inhibitors of GSK3 and PP1 can be considered to potentiate human sperm motility.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
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| Enthalten in: |
The world journal of men's health - 42(2024), 2 vom: 08. Apr., Seite 373-383 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Park, Seung Hyun [VerfasserIn] |
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| Links: |
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| Themen: |
Glycogen synthase kinase 3 |
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| Anmerkungen: |
Date Revised 02.04.2024 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.5534/wjmh.230004 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM361334532 |
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| 100 | 1 | |a Park, Seung Hyun |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Regulation of Phosphorylation of Glycogen Synthase Kinase 3α and the Correlation with Sperm Motility in Human |
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| 500 | |a Date Revised 02.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Copyright © 2024 Korean Society for Sexual Medicine and Andrology. | ||
| 520 | |a PURPOSE: To unravel the mechanism regulating the phosphorylation of glycogen synthase kinase 3 (GSK3) and the correlation between the inhibitory phosphorylation of GSK3α and sperm motility in human | ||
| 520 | |a MATERIALS AND METHODS: The phosphorylation and priming phosphorylated substrate-specific kinase activity of GSK3 were examined in human spermatozoa with various motility conditions | ||
| 520 | |a RESULTS: In human spermatozoa, GSK3α/β was localized in the head, midpiece, and principal piece of tail and p-GSK3α(Ser21) was enriched in the midpiece. The ratio of p-GSK3α(Ser21)/GSK3α was positively coupled with normal sperm motility criteria of World Health Organization. In high-motility spermatozoa, p-GSK3α(Ser21) phosphotyrosine (p-Tyr) proteins but p-GSK3α(Tyr279) markedly increased together with decreased kinase activity of GSK3 after incubation in Ca2+ containing medium. In high-motility spermatozoa, p-GSK3α(Ser21) levels were negatively coupled with kinase activity of GSK3, and which was deregulated in low-motility spermatozoa. In high-motility spermatozoa, 6-bromo-indirubin-3'-oxime, an inhibitor of kinase activity of GSK3 increased p-GSK3α(Ser21) and p-Tyr proteins. p-GSK3α(Ser21) and p-Tyr protein levels were decreased by inhibition of PKA and Akt. Calyculin A, a protein phosphatase-1/2A inhibitor, markedly increased the p-GSK3α(Ser21) and p-Tyr proteins, and significantly increased the motility of low-motility human spermatozoa | ||
| 520 | |a CONCLUSIONS: Down regulation of kinase activity of GSK3α by inhibitory phosphorylation was positively coupled with human sperm motility, and which was regulated by Ca2+, PKA, Akt, and PP1. Small-molecule inhibitors of GSK3 and PP1 can be considered to potentiate human sperm motility | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Glycogen synthase kinase 3 | |
| 650 | 4 | |a Humans | |
| 650 | 4 | |a Phosphorylation | |
| 650 | 4 | |a Sperm motility | |
| 700 | 1 | |a Kim, Young-Pil |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Jeong Min |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Dong-Wook |e verfasserin |4 aut | |
| 700 | 1 | |a Seo, Ju Tae |e verfasserin |4 aut | |
| 700 | 1 | |a Gye, Myung Chan |e verfasserin |4 aut | |
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