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PPT1 regulation of HSP90α depalmitoylation participates in the pathogenesis of hyperandrogenism

Ovarian granulosa cells (GCs) in the follicle are the important mediator of steroidogenesis and foster oocyte maturation. Evidences suggested that the function of GCs could be regulated by S-palmitoylation. However, the role of S-palmitoylation of GCs in ovarian hyperandrogenism remains elusive. Her...

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Autores principales: Xue, Tongmin, Zhao, Shanmeizi, Zhang, Hong, Tang, Ting, Zheng, Lu, Jing, Jun, Ge, Xie, Ma, Rujun, Ma, Jinzhao, Ren, Xiaoyan, Jueraitetibaike, Kadiliya, Guo, Zhigang, Chen, Li, Yao, Bing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9984558/
https://www.ncbi.nlm.nih.gov/pubmed/36879822
http://dx.doi.org/10.1016/j.isci.2023.106131
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author Xue, Tongmin
Zhao, Shanmeizi
Zhang, Hong
Tang, Ting
Zheng, Lu
Jing, Jun
Ge, Xie
Ma, Rujun
Ma, Jinzhao
Ren, Xiaoyan
Jueraitetibaike, Kadiliya
Guo, Zhigang
Chen, Li
Yao, Bing
author_facet Xue, Tongmin
Zhao, Shanmeizi
Zhang, Hong
Tang, Ting
Zheng, Lu
Jing, Jun
Ge, Xie
Ma, Rujun
Ma, Jinzhao
Ren, Xiaoyan
Jueraitetibaike, Kadiliya
Guo, Zhigang
Chen, Li
Yao, Bing
author_sort Xue, Tongmin
collection PubMed
description Ovarian granulosa cells (GCs) in the follicle are the important mediator of steroidogenesis and foster oocyte maturation. Evidences suggested that the function of GCs could be regulated by S-palmitoylation. However, the role of S-palmitoylation of GCs in ovarian hyperandrogenism remains elusive. Here, we demonstrated that the protein from GCs in ovarian hyperandrogenism phenotype mouse group exhibits lower palmitoylation level compared with that in the control group. Using S-palmitoylation-enriched quantitative proteomics, we identified heat shock protein isoform α (HSP90α) with lower S-palmitoylation levels in ovarian hyperandrogenism phenotype group. Mechanistically, S-palmitoylation of HSP90α modulates the conversion of androgen to estrogens via the androgen receptor (AR) signalling pathway, and its level is regulated by PPT1. Targeting AR signaling by using dipyridamole attenuated ovarian hyperandrogenism symptoms. Our data help elucidate ovarian hyperandrogenism from perspective of protein modification and provide new evidence showing that HSP90α S-palmitoylation modification might be a potential pharmacological target for ovarian hyperandrogenism treatment.
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spelling pubmed-99845582023-03-05 PPT1 regulation of HSP90α depalmitoylation participates in the pathogenesis of hyperandrogenism Xue, Tongmin Zhao, Shanmeizi Zhang, Hong Tang, Ting Zheng, Lu Jing, Jun Ge, Xie Ma, Rujun Ma, Jinzhao Ren, Xiaoyan Jueraitetibaike, Kadiliya Guo, Zhigang Chen, Li Yao, Bing iScience Article Ovarian granulosa cells (GCs) in the follicle are the important mediator of steroidogenesis and foster oocyte maturation. Evidences suggested that the function of GCs could be regulated by S-palmitoylation. However, the role of S-palmitoylation of GCs in ovarian hyperandrogenism remains elusive. Here, we demonstrated that the protein from GCs in ovarian hyperandrogenism phenotype mouse group exhibits lower palmitoylation level compared with that in the control group. Using S-palmitoylation-enriched quantitative proteomics, we identified heat shock protein isoform α (HSP90α) with lower S-palmitoylation levels in ovarian hyperandrogenism phenotype group. Mechanistically, S-palmitoylation of HSP90α modulates the conversion of androgen to estrogens via the androgen receptor (AR) signalling pathway, and its level is regulated by PPT1. Targeting AR signaling by using dipyridamole attenuated ovarian hyperandrogenism symptoms. Our data help elucidate ovarian hyperandrogenism from perspective of protein modification and provide new evidence showing that HSP90α S-palmitoylation modification might be a potential pharmacological target for ovarian hyperandrogenism treatment. Elsevier 2023-02-03 /pmc/articles/PMC9984558/ /pubmed/36879822 http://dx.doi.org/10.1016/j.isci.2023.106131 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Xue, Tongmin
Zhao, Shanmeizi
Zhang, Hong
Tang, Ting
Zheng, Lu
Jing, Jun
Ge, Xie
Ma, Rujun
Ma, Jinzhao
Ren, Xiaoyan
Jueraitetibaike, Kadiliya
Guo, Zhigang
Chen, Li
Yao, Bing
PPT1 regulation of HSP90α depalmitoylation participates in the pathogenesis of hyperandrogenism
title PPT1 regulation of HSP90α depalmitoylation participates in the pathogenesis of hyperandrogenism
title_full PPT1 regulation of HSP90α depalmitoylation participates in the pathogenesis of hyperandrogenism
title_fullStr PPT1 regulation of HSP90α depalmitoylation participates in the pathogenesis of hyperandrogenism
title_full_unstemmed PPT1 regulation of HSP90α depalmitoylation participates in the pathogenesis of hyperandrogenism
title_short PPT1 regulation of HSP90α depalmitoylation participates in the pathogenesis of hyperandrogenism
title_sort ppt1 regulation of hsp90α depalmitoylation participates in the pathogenesis of hyperandrogenism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9984558/
https://www.ncbi.nlm.nih.gov/pubmed/36879822
http://dx.doi.org/10.1016/j.isci.2023.106131
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