ferritin heavy chain
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2021 ◽  
pp. 074823372110485
Author(s):  
Yu Hu ◽  
Lei Wu ◽  
San-Qiao Yang ◽  
Hai-Jun Wei ◽  
Chun-Yan Wang ◽  
...  

Formaldehyde (FA) causes neurotoxicity and contributes to the occurrence of neurodegenerative diseases. However, the mechanism of FA-induced neurotoxicity has not been fully elucidated. Ferritinophagy, an autophagy process of ferritin mediated by the nuclear receptor coactivator 4 (NCOA4), is a potential mechanism of neurotoxicity. In this study, we explored whether ferritinophagy is associated with the neurotoxicity of FA. Our results showed that FA (50, 100, 200 μM; 24 h) exposure upregulated ferritinophagy in the mouse hippocampal neuronal HT22 cells, which was evidenced by the upregulated autophagic flux, the increased colocalizations of NCOA4 with ferritin heavy chain (FTH1) and NCOA4 with microtubule-associated protein 1 light chain-3B (LC3B), the augmented expression of NCOA4, and the reduced content of FTH1. We also found that FA (0.1, 1, and 10 μmol, i.c.v., 7d) administration boosted ferritinophagy in the hippocampus of Sprague-Dawley (SD) rats, which was demonstrated by the accumulated autophagosomes, the increased expressions of LC3II/I and NCOA4, and the decreased contents of p62 and FTH1 in the hippocampus. Further, we confirmed that inhibition of ferritinophagy by silencing the expression of NCOA4 decreased FA-induced toxic damage in HT22 cells. These results indicated that FA induces neurotoxicity by promoting ferritinophagy. Our findings suggest a potential mechanism insight into the FA-induced neurotoxicity, which in turn provides a new thought for the treatment of FA-related neurodegenerative diseases.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Luca Tirinato ◽  
Maria Grazia Marafioti ◽  
Francesca Pagliari ◽  
Jeannette Jansen ◽  
Ilenia Aversa ◽  
...  

Although much progress has been made in cancer treatment, the molecular mechanisms underlying cancer radioresistance (RR) as well as the biological signatures of radioresistant cancer cells still need to be clarified. In this regard, we discovered that breast, bladder, lung, neuroglioma and prostate 6 Gy X-ray resistant cancer cells were characterized by an increase of Lipid Droplet (LD) number and that the cells containing highest LDs showed the highest clonogenic potential after irradiation. Moreover, we observed that LD content was tightly connected with the iron metabolism and in particular with the presence of the ferritin heavy chain (FTH1). In fact, breast and lung cancer cells silenced for the FTH1 gene showed a reduction in the LD numbers and, by consequence, became radiosensitive. FTH1 overexpression as well as iron-chelating treatment by Deferoxamine were able to restore the LD amount and RR. Overall, these results provide evidence of a novel mechanism behind RR in which LDs and FTH1 are tightly connected to each other, a synergistic effect which might be worth deeply investigating in order to make cancer cells more radiosensitive and improve the efficacy of radiation treatments.


Author(s):  
Harpreet Kaur ◽  
William S. Bush ◽  
Scott L. Letendre ◽  
Ronald J. Ellis ◽  
Robert K. Heaton ◽  
...  

2021 ◽  
Author(s):  
Cuixiu Lu ◽  
Huijun Zhao ◽  
Man Zhang

Abstract Ferritin is an important molecule in the regulation of cell proliferation, growth inhibition escape, cell death inhibition and angiogenesis. More and more studies have given evidence of abnormal iron metabolism in tumors. Whether ferritin can be a new type of marker for early diagnosis of tumorous diseases remains to be explored. In this study, we verified the expression level of ferritin heavy chain (FTH) in benign prostatic hyperplasia epithelial cell (BPH-1) and three kinds of PCa cells by Western blotting. Lentivirus was used to construct FTH gene overexpression vector, then construct FTH overexpression PCa cell lines. Meanwhile, LNCaP cells and DU145 cells FTH silent expression prostate cancer cell lines were constructed using Crispr Cas9 technology. Next, clone proliferation experiments, transwell experiments, and scratch experiments were used to verify the cell proliferation, invasion, and migration capabilities of each group of cells with different FTH expression levels. The FTH knockout PC-3 cell (LV-shFTH PC3) has been established in our laboratory. Make full use of the existing results from Isobaric Tag for Relative and Absolute Quantitation (iTRAQ) mass spectrometry technology to analyze differentially expressed protein analysis between LV-shFTH PC3 cells and control cells. Combine GO analysis to select the target protein for subsequent cell protein expression level verification. Our results show that FTH overexpression can promote the proliferation, migration and invasion of prostate cancer cell lines, while FTH knockout causes the opposite result. Combined with mass spectrometry (MS) detection, it is speculated that FTH may trigger changes in cell behavior by regulating the expression of the following proteins: S100A4, CRABP1, S100A2, S100P, GDF15, FAM84B, KRT75, LYRM7, OCLN, LCP1, F2RL1. (The study is not a clinical trial, no registration number and registration date are required)


2021 ◽  
Author(s):  
Luca Tirinato ◽  
Maria Grazia Marafioti ◽  
Francesca Pagliari ◽  
Jeanette Jansen ◽  
Ilenia Aversa ◽  
...  

Although much progress has been made in cancer treatment, the molecular mechanisms underlying cancer radioresistance (RR) as well as the biological characteristic of radioresistant cancer cells still need to be clarified. In this regard, we discovered that breast, bladder, lung, neuroglioma and prostate 6 Gy X-ray resistant cells were characterized by an increase of Lipid Droplet (LD) number and that the cells containing highest LDs showed the highest clonogenic potential after irradiation. Moreover, we observed that LD content was tightly connected with the iron metabolism and in particular with the presence of the ferritin heavy chain (FTH1). In fact, breast and lung cancer cells silenced for the FTH1 gene showed a reduction in the LD numbers and, by consequence, became radiosensitive. FTH1 restoration as well as iron-chelating treatment by Deferoxamine were able to restore the LD amount and RR. Overall, these results provide evidence of a novel molecular mechanism behind RR in which LDs and FTH1 are tightly connected to each other, a synergistic effect which might be worth deeply investigating in order to make cancer cells more radiosensitive and improve the efficacy of radiation treatments.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Zifeng Huang ◽  
Wenwen Si ◽  
Xinrong Li ◽  
Shanyu Ye ◽  
Xuelei Liu ◽  
...  

Ferroptosis is associated with neural degeneration of dopaminergic neurons in Parkinson’s disease (PD). However, how to control the level of ferroptosis in PD remains unclear. Clinically, moxibustion has been used to treat PD and has an apparent therapeutic effect on improving the motor symptoms of PD. In the present study, the PD rat model was constructed by two-point stereotactic 6-hydroxydopamine injection. Then, moxibustion was used to treat the PD rats. The expression of glutathione peroxidase 4 (GPX4) and Ferritin Heavy Chain 1 (FTH1), the level of reactive oxygen species (ROS), and the morphology of mitochondrial were detected to evaluate the level of ferroptosis. The results showed that moxibustion treatment of Shi’s moxa sticks could reduce the behavioral score, alleviate the level of ferroptosis, decrease mitochondrial damage, and improve dopaminergic neuron survival. In conclusion, the present study results indicated that Shi’s moxa sticks could effectively suppress the level of ferroptosis, thereby improving the survival of dopaminergic neurons in the SNpc of PD rats, which may provide a promising complementary and alternative therapy for PD patients.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Adam N. Goldfarb ◽  
Katie C. Freeman ◽  
Ranjit K. Sahu ◽  
Kamaleldin E. Elagib ◽  
Maja Holy ◽  
...  

AbstractAnemias of chronic disease and inflammation (ACDI) result from restricted iron delivery to erythroid progenitors. The current studies reveal an organellar response in erythroid iron restriction consisting of disassembly of the microtubule cytoskeleton and associated Golgi disruption. Isocitrate supplementation, known to abrogate the erythroid iron restriction response, induces reassembly of microtubules and Golgi in iron deprived progenitors. Ferritin, based on proteomic profiles, regulation by iron and isocitrate, and putative interaction with microtubules, is assessed as a candidate mediator. Knockdown of ferritin heavy chain (FTH1) in iron replete progenitors induces microtubule collapse and erythropoietic blockade; conversely, enforced ferritin expression rescues erythroid differentiation under conditions of iron restriction. Fumarate, a known ferritin inducer, synergizes with isocitrate in reversing molecular and cellular defects of iron restriction and in oral remediation of murine anemia. These findings identify a cytoskeletal component of erythroid iron restriction and demonstrate potential for its therapeutic targeting in ACDI.


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