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

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number108922
JournalCell Reports
Volume34
Issue number13
DOIs
StatePublished - Mar 30 2021
Externally publishedYes

Keywords

  • GSNOR
  • hematopoietic stem cell
  • nitric oxide
  • protein aggregation
  • regeneration
  • S-nitrosylation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint

Dive into the research topics of 'Protein S-nitrosylation regulates proteostasis and viability of hematopoietic stem cell during regeneration'. Together they form a unique fingerprint.

Cite this