Dietary methionine supplementation promotes mice hematopoiesis after irradiation DOI Creative Commons
Weiwei Zhang, Yang Xiang, Qiang Chen

et al.

Military Medical Research, Journal Year: 2024, Volume and Issue: 11(1)

Published: Dec. 20, 2024

Abstract Background With the increasing risk of nuclear exposure, more attention has been paid to prevention and treatment acute radiation syndrome (ARS). Although amino acids are key nutrients involved in hematopoietic regulation, impacts on bone marrow hematopoiesis following irradiation associated mechanisms have not fully elucidated. Hence, it is paramount importance study changes acid metabolism after their effects as well related mechanisms. Methods The content serum was analyzed using metabolomic sequencing. survival rate body weight irradiated mice were detected altering methionine diet. Extracellular matrix (ECM) protein analysis performed via proteomics analysis. Inflammatory factors examined by enzyme-linked immunosorbent assay (ELISA). Flow cytometry, Western blotting, immunofluorescence employed determine mechanism which S100 calcium-binding A4 (S100A4) regulates macrophage polarization. Results time significantly with alterations multiple acids, particularly methionine. A high diet promoted tolerance, especially recovery hematopoiesis, yet dose limitations. Folate could partially alleviate bottleneck reducing accumulation homocysteine. Mechanistically, levels maintained abundance ECM components, including collagens glycoproteins, post-irradiation, among level S100A4 changed. regulated polarization STAT3 pathway, inhibited inflammation facilitated proliferation differentiation stem/progenitor cells. Conclusions We demonstrated that an appropriate elevation dietary enhances tolerance explains irradiation.

Language: Английский

Inhibition of DEK restores hematopoietic stem cell function in Fanconi anemia DOI

Zhe Chen,

Feng Wu, Yan Li

et al.

The Journal of Experimental Medicine, Journal Year: 2025, Volume and Issue: 222(3)

Published: Jan. 21, 2025

Hematopoietic stem cells (HSCs) are susceptible to replication stress, which is a major contributor HSC defects in Fanconi anemia (FA). Here, we report that HSCs relax the global chromatin by downregulating expression of architectural protein, DEK, response stress. DEK abnormally accumulated bone marrow (BM) CD34+ from patients with FA and Fancd2-deficient HSCs. haploinsufficiency promotes relaxation, stress relief, function recovery Furthermore, inhibition restores proliferation vitro enhances their engraftment vivo. Mechanistically, activating transcription factor 2 (ATF2), specifically phosphorylated ATF2 at Thr69/71, was identified as promoter transcription. Fancd2 deficiency results p38 hyperphosphorylation, turn phosphorylates leading accumulation In conclusion, our findings establish functional link between relaxation tolerance highlight target for FA.

Language: Английский

Citations

0
Advances in the Regulation of Hematopoietic Homeostasis by Programmed Cell Death Under Radiation Conditions DOI
Manling Shu, Jinfu Zhang, Haiyun Huang

et al.

Stem Cell Reviews and Reports, Journal Year: 2025, Volume and Issue: unknown

Published: March 8, 2025

Language: Английский

Citations

0
Phosphorylation of eIF2α suppresses the impairment of GSH/NADPH homeostasis and mitigates the activation of cell death pathways, including ferroptosis, during ER stress DOI Open Access
Lê Thị Thu Hiền, Yong Hwan Kim, Mi Jeong Kim

et al.

Molecules and Cells, Journal Year: 2025, Volume and Issue: unknown, P. 100210 - 100210

Published: March 1, 2025

eIF2α phosphorylation helps maintain cellular homeostasis and overcome endoplasmic reticulum (ER) stress through transcriptional translational reprogramming. This study aims to elucidate the regulation of glutathione (GSH) NADPH its impact on cell death during ER stress. phosphorylation-deficient (A/A) cells exhibited decreased expression multiple genes involved in GSH synthesis production, leading an exacerbated depletion both mitochondrial GSH, as well NADPH, Impaired resulted from deficient ATF4 and/or dependent factor, Nrf2, which are key transcription factors antioxidant response In contrast, exacerbation may primarily be attributed dysregulated serine-driven one-carbon metabolism pathway genes, regulated by unidentified phosphorylation-dependent mechanism Moreover, phosphorylation-ATF4 axis was responsible for upregulation ferroptosis-inhibiting downregulation ferroptosis-activating upon Therefore, strongly induced ferroptosis A/A cells, significantly inhibited treatments with cell-permeable inhibitor ferrostatin-1 (Fer-1). overexpression suppressed impairment promoting downstream target genes. Consequently, mitigated apoptosis Our findings underscore importance maintaining GSH/NADPH inhibiting target(s)-mediated reprogramming

Language: Английский

Citations

0
Ferumoxytol promotes haematopoietic stem cell post-injury regeneration as a reactive oxygen species scavenger DOI
Qiwei Wang, Wenchang Qian, Yingli Han

et al.

Nature Nanotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: April 23, 2025

Language: Английский

Citations

0
Dietary methionine supplementation promotes mice hematopoiesis after irradiation DOI Creative Commons
Weiwei Zhang, Yang Xiang, Qiang Chen

et al.

Military Medical Research, Journal Year: 2024, Volume and Issue: 11(1)

Published: Dec. 20, 2024

Abstract Background With the increasing risk of nuclear exposure, more attention has been paid to prevention and treatment acute radiation syndrome (ARS). Although amino acids are key nutrients involved in hematopoietic regulation, impacts on bone marrow hematopoiesis following irradiation associated mechanisms have not fully elucidated. Hence, it is paramount importance study changes acid metabolism after their effects as well related mechanisms. Methods The content serum was analyzed using metabolomic sequencing. survival rate body weight irradiated mice were detected altering methionine diet. Extracellular matrix (ECM) protein analysis performed via proteomics analysis. Inflammatory factors examined by enzyme-linked immunosorbent assay (ELISA). Flow cytometry, Western blotting, immunofluorescence employed determine mechanism which S100 calcium-binding A4 (S100A4) regulates macrophage polarization. Results time significantly with alterations multiple acids, particularly methionine. A high diet promoted tolerance, especially recovery hematopoiesis, yet dose limitations. Folate could partially alleviate bottleneck reducing accumulation homocysteine. Mechanistically, levels maintained abundance ECM components, including collagens glycoproteins, post-irradiation, among level S100A4 changed. regulated polarization STAT3 pathway, inhibited inflammation facilitated proliferation differentiation stem/progenitor cells. Conclusions We demonstrated that an appropriate elevation dietary enhances tolerance explains irradiation.

Language: Английский

Citations

0