unveiling-phosphorylation-modification-using-phos-tag-sds-page-gel

Unveiling Phosphorylation Modification Using Phos-tag SDS-PAGE Gel Electrophoresis and <em>In Vitro</em> Kinase Assay

Phosphorylation is a classic post-translational modification that regulates protein function. Proteins typically contain multiple potential ...

Medical School of Nanjing University

Iron accumulation in the central nervous system (CNS) is a common feature of many neurodegenerative diseases. Multicopper ferroxidases (MCFs) play an important role in cellular iron metabolism. However, the role of MCFs in the CNS in health and disease remains poorly characterized.

Hephaestin and ceruloplasmin play distinct but interrelated roles in iron homeostasis in mouse brain.

Multicopper ferroxidases (MCFs) play an important role in cellular iron homeostasis. However, the role of MCFs in renal metabolism remains unclear. We used Hephaestin (Heph) and Ceruloplasmin (Cp) single or double (Heph/Cp) knockout (KO) mice to study the roles of MCFs in the kidney. Renal iron levels and the expression of iron metabolism genes were examined. The non-heme iron content both in the renal cortex and medulla of Heph/Cp KO mice was significantly increased. Perls' Prussian blue staining showed iron accumulation on the apical side of renal tubular cells in Heph/Cp KO mice. A significant increase in ferritin protein expression was also observed in the renal medulla and cortex of Heph/Cp KO mice. Both DMT1 and TfR1 protein expression were significantly decreased in the renal medulla of Heph/Cp KO mice, while the expression of DMT1 protein was significantly increased in the renal cortex of these animals. Significant increase in proteinuria and total urinary iron was observed in the double knockout mice, and this was associated with compromised structural integrity. These results suggest that KO of both the HEPH and CP genes leads to kidney iron deposition and toxicity, MCFs could protect kidney against a damage from iron excess.

Hephaestin and ceruloplasmin facilitate iron metabolism in the mouse kidney.

A receptive endometrium is essential for maternal-embryonic molecular communication during implantation. However, the specific molecular regulatory mechanisms of the endometrial capacity remain poorly understood. Here, we examined activating transcription factor 3 (ATF3) expression in human endometria and the functional effect of ATF3 on embryo attachment in vitro.

Activating transcription factor 3 promotes embryo attachment via up-regulation of leukemia inhibitory factor in vitro.

The accumulation of iron occurs in the central nervous system (CNS) in several neurodegenerative diseases. Although multi-copper ferroxidases (MCFs) play an important role in cellular iron metabolism and homeostasis, the mechanism of MCFs in the CNS remains unclear.

Multi-Copper Ferroxidase-Deficient Mice Have Increased Brain Iron Concentrations and Learning and Memory Deficits.

Accumulation of iron has been associated with the pathobiology of various disorders of the central nervous system. Our previous work has shown that hephaestin (Heph) and ceruloplasmin (Cp) double knockout (KO) mice induced iron accumulation in multiple brain regions and that this was paralleled by increased oxidative damage and deficits in cognition and memory. In this study, we enriched astrocytes and oligodendrocytes from the cerebral cortex of neonatal wild-type (WT), Heph KO and Cp KO mice. We demonstrated that Heph is highly expressed in oligodendrocytes, while Cp is mainly expressed in astrocytes. Iron efflux was impaired in Cp KO astrocytes and Heph KO oligodendrocytes and was associated with increased oxidative stress. The expression of Heph, Cp, and other iron-related genes was examined in astrocytes and oligodendrocytes both with and without iron treatment. Interestingly, we found that the expression of the mRNA encoding ferroportin 1, a transmembrane protein that cooperates with CP and HEPH to export iron from cells, was positively correlated with Cp expression in astrocytes, and with Heph expression in oligodendrocytes. Our findings collectively demonstrate that HEPH and CP are important for the prevention of glial iron accumulation and thus may be protective against oxidative damage.

Multi-copper ferroxidase deficiency leads to iron accumulation and oxidative damage in astrocytes and oligodendrocytes.

Our understanding of the relationship between stress-derived epinephrine and early pregnancy failure remains incomplete. Here, we explored the effect of epinephrine exposure on early pregnancy and pseudopregnancy in mice. Increased expression of adrenergic receptors Adra1b, Adra2b and Adrb2 was observed during decidualization and post-implantation embryogenesis was delayed or survival impaired. Epinephrine treatment also impaired decidualization in both the gravid and pseudopregnant uterus, suggesting the effect on decidualization was independent of the conceptus. This included a suppression of endometrial stroma cell proliferation and of key decidualization regulators, including COX2, BMP2 and WNT4. Collectively, these data demonstrate that maternal epinephrine exposure during early pregnancy impairs uterine decidualization and embryo development, underlying early pregnancy failure.

An exaggerated epinephrine-adrenergic receptor signaling impairs uterine decidualization in mice.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has infected millions of people around the world. Vaccination is a pillar in the strategy to control transmission of the SARS-CoV-2 spread. Immune responses to vaccination require elucidation.

Article	Year
Hephaestin and ceruloplasmin play distinct but interrelated roles in iron homeostasis in mouse brain. The Journal of nutrition\| PubMed ID: 25788583	2015
Hephaestin and ceruloplasmin facilitate iron metabolism in the mouse kidney. Scientific reports\| PubMed ID: 27991585	2016
Activating transcription factor 3 promotes embryo attachment via up-regulation of leukemia inhibitory factor in vitro. Reproductive biology and endocrinology : RB&E\| PubMed ID: 28577574	2017
Multi-Copper Ferroxidase-Deficient Mice Have Increased Brain Iron Concentrations and Learning and Memory Deficits. The Journal of nutrition\| PubMed ID: 29659961	2018
Multi-copper ferroxidase deficiency leads to iron accumulation and oxidative damage in astrocytes and oligodendrocytes. Scientific reports\| PubMed ID: 31263155	2019
An exaggerated epinephrine-adrenergic receptor signaling impairs uterine decidualization in mice. Reproductive toxicology (Elmsford, N.Y.)\| PubMed ID: 31520687	2019
Protective antigenic epitopes revealed by immunosignatures after three doses of inactivated SARS-CoV-2 vaccine. Frontiers in immunology\| PubMed ID: 36016943	2022

Ruiwei Jiang

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