Article ; Online: Bu-Shen-Zhu-Yun decoction induces PRLR deubiquitination and JAK2/STAT5 activation via CSN5
Aging
2021 Volume 13, Issue 16, Page(s) 20418–20437
Abstract: Purpose: To determine the effect of Bu-Shen-Zhu-Yun Decoction (BSZY-D) on the kisspeptin through JAK2/STAT5 signaling pathway in hyperprolactinemia (HPRL) infertility.: Method: SD rats were treated with BSZY-D for cerebrospinal fluid (CSF) extraction. ...
| Abstract | Purpose: To determine the effect of Bu-Shen-Zhu-Yun Decoction (BSZY-D) on the kisspeptin through JAK2/STAT5 signaling pathway in hyperprolactinemia (HPRL) infertility. Method: SD rats were treated with BSZY-D for cerebrospinal fluid (CSF) extraction. GT1-7 cells were subjected to different treatments. The phosphorylation levels of JAK2 and STAT5, and the expressions of PRLR and kisspeptin of GT1-7 cells in different groups were detected by western blot, RT-qPCR and immunofluorescence. The expressions of CSN5 and GATA1 and other molecular features were checked by western blot, RT-PCR, co-immunoprecipitation and renilla luciferase activity. Results: The phosphorylation levels of JAK2 and STAT5, and the expressions of PRLR and kisspeptin in the HPRL group were significantly decreased, and these changes could be reversed after BSZY-D treatment. In addition, the presence of PRLR deubiquitination was detected in the HPRL group, which could be reversed by shRNA-CSN5, suggesting that BSZY-D played a role through targeting CSN5. The binding level of GATA1 and CSN5 promoter in the HPRL group was significantly decreased, but elevated in the HPRL (BSZY-D/CSF) group (P < 0.05). Conclusion: BSZY-D improved the transcription activity of GATA1 and increased the binding of GATA1 and CSN5. BSZY-D was involved in the deubiquitination of PRLR, which contributes to alleviating the symptoms of HPRL infertility. |
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| MeSH term(s) | Animals ; COP9 Signalosome Complex/genetics ; COP9 Signalosome Complex/metabolism ; Drugs, Chinese Herbal/administration & dosage ; Female ; GATA1 Transcription Factor/genetics ; GATA1 Transcription Factor/metabolism ; Humans ; Hyperprolactinemia/drug therapy ; Hyperprolactinemia/genetics ; Hyperprolactinemia/metabolism ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Janus Kinase 2/genetics ; Janus Kinase 2/metabolism ; Prolactin/genetics ; Prolactin/metabolism ; Rats ; Rats, Sprague-Dawley ; STAT5 Transcription Factor/genetics ; STAT5 Transcription Factor/metabolism ; Signal Transduction/drug effects |
| Chemical Substances | Drugs, Chinese Herbal ; GATA1 Transcription Factor ; Gata1 protein, rat ; Gps1 protein, rat ; Intracellular Signaling Peptides and Proteins ; STAT5 Transcription Factor ; Prolactin (9002-62-4) ; Jak2 protein, rat (EC 2.7.10.2) ; Janus Kinase 2 (EC 2.7.10.2) ; COP9 Signalosome Complex (EC 3.4.19.12) |
| Language | English |
| Publishing date | 2021-08-23 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ISSN | 1945-4589 |
| ISSN (online) | 1945-4589 |
| DOI | 10.18632/aging.203426 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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