Protein S-nitrosylation regulates proteostasis and viability of hematopoietic stem cell during regeneration

Weiwei Yi, Yuying Zhang, Bo Liu, Yuanyuan Zhou, Dandan Liao, Xinhua Qiao, Dan Gao, Ting Xie, Qin Yao, Yao Zhang, Yugang Qiu, Gang Huang, Zhiyang Chen, Chang Chen, Zhenyu Ju

Producción científica: Articlerevisión exhaustiva

18 Citas (Scopus)

Resumen

Hematopoietic stem cells (HSCs) regenerate blood cells upon hematopoietic injuries. During homeostasis, HSCs are maintained in a low reactive oxygen species (ROS) state to prevent exhaustion. However, the role of nitric oxide (NO) in controlling HSC regeneration is still unclear. Here, we find increased NO during HSC regeneration with an accumulation of protein aggregation. S-nitrosoglutathione reductase (GSNOR)-deleted HSCs exhibit a reduced reconstitution capacity and loss of self-renewal after chemotherapeutic injury, which is resolved by inhibition of NO synthesis. Deletion of GSNOR enhances protein S-nitrosylation, resulting in an accumulation of protein aggregation and activation of unfolded protein response (UPR). Treatment of taurocholic acid (TCA), a chemical chaperone, rescues the regeneration defect of Gsnor−/− HSCs after 5-fluorouracil (5-FU) treatment. Deletion of C/EBP homologous protein (Chop) restores the reconstitution capacity of Gsnor−/− HSCs. These findings establish a link between S-nitrosylation and protein aggregation in HSC in the context of blood regeneration.

Idioma originalEnglish (US)
Número de artículo108922
PublicaciónCell Reports
Volumen34
N.º13
DOI
EstadoPublished - mar 30 2021
Publicado de forma externa

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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