The IL-27 component EBI-3 and its receptor subunit IL-27Rα are essential for the cytoprotective action of humanin on male germ cells†
In: Biology of Reproduction, Jg. 104 (2020-12-16), S. 717-730
Online
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Zugriff:
Humanin (HN) is a mitochondrial-derived peptide that protects many cells/tissues from damage. We previously demonstrated that HN reduces stress-induced male germ cell apoptosis in rodents. HN action in neuronal cells is mediated through its binding to a trimeric cell membrane receptor composed of glycoprotein 130 (gp130), IL-27 receptor subunit (IL-27R, also known as WSX-1/TCCR), and ciliary neurotrophic factor receptor subunit (CNTFR). The mechanisms of HN action in testis remain unclear. We demonstrated in ex-vivo seminiferous tubules culture that HN prevented heat-induced germ cell apoptosis was blocked by specific anti-IL-27R, anti-gp130, and anti-EBI-3, but not by anti-CNTFR antibodies significantly. The cytoprotective action of HN was studied by using groups of il-27r−/− or ebi-3−/− mice administered the following treatment: (1) vehicle; (2) a single intraperitoneal (IP) injection of HN peptide; (3) testicular hyperthermia; and (4) testicular hyperthermia plus HN. We demonstrated that HN inhibited heat-induced germ cell apoptosis in wildtype but not in il-27r−/− or ebi-3−/− mice. HN restored heat-suppressed STAT3 phosphorylation in wildtype but not il-27r−/− or ebi-3−/− mice. Dot blot analyses showed the direct interaction of HN with IL-27R or EBI-3 peptide. Immunofluorescence staining showed the co-localization of IL-27R with HN and gp130 in Leydig cells and germ cells. We conclude that the anti-apoptotic effects of HN in mouse testes are mediated through interaction with EBI-3, IL-27R, and activation of gp130, whereas the role of CNTFR needs further studies. This suggests a multicomponent tissue-specific receptor for HN in the testis and links HN action with the IL-12/IL-27 family of cytokines.
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The IL-27 component EBI-3 and its receptor subunit IL-27Rα are essential for the cytoprotective action of humanin on male germ cells†
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Autor/in / Beteiligte Person: | Surampudi, Prasanth ; Cohen, Pinchas ; Lue, Yanhe ; Swerdloff, Ronald S. ; Wang, Christina ; Dai-Ju, Jenny ; Jia, Yue |
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Zeitschrift: | Biology of Reproduction, Jg. 104 (2020-12-16), S. 717-730 |
Veröffentlichung: | Oxford University Press (OUP), 2020 |
Medientyp: | unknown |
ISSN: | 1529-7268 (print) ; 0006-3363 (print) |
DOI: | 10.1093/biolre/ioaa225 |
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