Dataset Information

Down-regulated Glutathione Peroxidase-4 by Graphene Quantum Dots Inducing Ferroptosis in Macrophages

ABSTRACT: to explore the mechanism, we analyzed the differences in the protein profile of macrophages using tandem mass tags (TMT) proteomics.

ORGANISM(S): Mus Musculus

SUBMITTER: Yi Huang

PROVIDER: PXD023303 | iProX | Wed Dec 23 00:00:00 GMT 2020

REPOSITORIES: iProX

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Publications

Increased lipid peroxidation by graphene quantum dots induces ferroptosis in macrophages.

Shao Yan Y Wang Liting L Chen Jiajia J Hunag Youying Y Huang Yiwei Y Wang Xiaoyang X Zhou Daxue D Zhang Jinqiang J Wu Wen W Zhang Qianyu Q Li Fei F Xia Xuefeng X Huang Yi Y

NanoImpact 20210615

Graphene quantum dots (GQDs) are an excellent tool for theranostics, and are widely used in nanomedical applications. The biosafety of GQDs has received abundant attention, but their latent toxicological mechanisms remain inadequately understood. To investigate the cellular and molecular mechanisms underlying graphene-mediated changes, quantitative proteomics and untargeted lipidomics were integrated. We discovered that glutathione peroxidase 4 as a key regulator of ferroptosis, was down-regulat ...[more]

PMID: 35559835

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Project description:High-altitude polycythemia (HAPC) is a chronic condition prevalent in individuals residing at high altitudes (HA), characterized by an augmented production of red blood cells (RBCs) due to hypoxic conditions. Despite its prevalence, the pathophysiological basis and molecular mechanisms driving HAPC remain largely unelucidated. In our study, we utilized a mouse model exposed to hypobaric hypoxia (HH), replicating the environmental conditions experienced at 6000 m above sea level, coupled with in vitro analysis of primary splenic macrophages under 1% O2 to investigate these mechanisms. Our findings revealed that HH exposure significantly stimulates erythropoiesis, leading to erythrocytosis. This was accompanied by a notable sequence of splenic changes, initially characterized by splenic contraction, which subsequently progressed to splenomegaly over 14 days. A key observation was the impairment on the capacity of spleen to process RBCs, primarily attributed to a reduction in splenic macrophages located in the red pulp. Extended HH treatment over 7 and 14 days precipitated increased iron mobilization and the onset of ferroptosis within the spleen. This was evidenced by altered expression levels of iron metabolism and ferroptosis-related proteins, paralleling gene expression patterns observed in human peripheral blood mononuclear cells. Single-cell sequencing of splenic tissue post-HH exposure demonstrated a marked decrease in macrophage populations after 7 days. Our study further disclosed a significant increase in RBCs retention in the spleen following HH exposure, likely a consequence of diminished red pulp macrophages (RPMs) and erythrophagocytosis. This hypothesis was corroborated through comprehensive analyses involving flow cytometry, histological staining, and immunostaining, which collectively provided a detailed understanding of RBCs dynamics under HH conditions. In vitro analyses substantiated the decline in primary splenic macrophages and induction of ferroptosis under hypoxic treatment, effects that were relieved by pre-treatment with the ferroptosis inhibitor ferrostatin-1. Collectively, our data suggest that HH exposure initiates splenic ferroptosis, leading primarily to a decrease in RPMs. This decrease potentially impacts erythrophagocytosis, contributing to increased RBCs retention and subsequent splenomegaly. Such changes could potentially foster continuous RBCs production and accelerate the progress of HAPC. In conclusion, our study highlights the important role of the spleen and splenic macrophages in the pathogenesis of HAPC, providing crucial insights into the disease progression and potential therapeutic targets.

Dataset Information

Down-regulated Glutathione Peroxidase-4 by Graphene Quantum Dots Inducing Ferroptosis in Macrophages

Publications

Increased lipid peroxidation by graphene quantum dots induces ferroptosis in macrophages.

Similar Datasets

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