Research progress on the role of HIFs-PHDs oxygen-sensing pathway in cellular ferroptosis / 生理学报

Hypoxia-inducible factors (HIFs) are one of the primary transcription factors regulating oxygen balance, and their stability is determined by the hydroxylation state of the prolyl hydroxylase domain (PHD) that is sensitive to oxygen. In recent years, studies have shown that HIFs-prolyl hydroxylases (PHDs) oxygen-sensing pathway is involved in the process of cellular ferroptosis. Ferroptosis, a new type of cell death, different from necrosis, apoptosis, necrotizing apoptosis, and pyroptosis, is essentially a programmed death caused by the accumulation of iron-dependent lipid peroxides in cells. This paper focuses on the role and mechanism of the HIFs-PHDs oxygen-sensing pathway in cellular ferroptosis involved in nerve diseases, tumors, lung injury, and chemical nerve damage from three aspects of iron metabolism, lipid metabolism, and glutathione (GSH) synthesis/metabolism. This review will provide a theoretical basis and new ideas for the development of novel drugs targeting the HIFs-PHDs oxygen-sensing pathway and capable of regulating ferroptosis for the treatment of diseases related to ferroptosis such as nervous system diseases and tumors.

Characteristics of autophagy and its effect on cell proliferation in giant cell tumor of bone / 临床与实验病理学杂志

Purpose To investigate the autophagy characteristics of giant cell tumor of bone and its effect on cell proliferation. Methods Giant cell tumors of bone (GCT-0404 cells) were cultured in vitro and treated with serum-starvation, rapamycin and inhibitor chloroquine. Western blot analysis was performed to detect the autophagic markers LC3 and Beclin 1 expression. Immunofluorescence method was used to show intracellular autophagy formation. Inverted microscope was used to observe the cell morphology. CCK-8 assays were used to detect the cell viability. Results Green fluorescent spots that represented the transformation level of LC3-I to LC3-Ⅱ increased significantly (P＜0.05) by serum-starvation, rapamycin and inhibitor chloroquine respectively, but the expression level of Beclin 1 was not raised. In addition, the cell morphology changed significantly, and cell proliferation was inhibited after serum-starvation, and treatment with rapamycin and inhibitor chloroquine (P＜0.05), Conclusion The changes of autophagy caused by serum starvation, rapamycin and inhibitor chloroquine in GCT-0404 cells may be involved in the down-regulation of cell proliferation.

Effects of acrylonitrile in drinking water on monoamine neurotransmitters and its metabolites in male rat brains / 中华预防医学杂志

<p><b>OBJECTIVES</b>To elucidate the possible involvement of monoamine neurotransmitters in the development of neurobehavioral damage produced by acrylonitrile in drinking water in male rat brains.</p><p><b>METHODS</b>Totally 30 male SD rats were randomly divided into three groups, the control group (n = 10), low dosage group (n = 10), and high dosage group (n = 10), which were respectively administered 0 mg/L, 50 mg/L, 200 mg/L acrylonitrile (AN) in drinking water. The treatment was lasted for 12 weeks. Seven animals were randomly selected from each group for determination of monoamine neurotransmitters in striatum and cerebellum by high performance liquid chromatography with electrochemical detector and activities of monoamine oxidase in cortex.</p><p><b>RESULTS</b>The contents of dopamine in the striatum of low and high dosage groups were decreased to (2.2 +/- 0.7) and (3.2 +/- 2.0) microg/g wet tissue, respectively, and compared with that of control group (9.0 +/- 4.2) microg/g wet tissue, the differences were statistically significant. There were no statistical differences among the contents of dopamine in the cerebellum of all rats, and the levels of 3,4-dihydroxyphenylacetic acid (DOPAC), the major metabolite of dopamine in the cerebellum were (186 +/- 41), (245 +/- 90) and (115 +/- 65) ng/g wet tissue in the control, low and high dosage groups, respectively and in low-dosage group they were significantly higher than those in other groups. There was dosage-dependently decreasing of the contents of serotonin of striatum in the control (249 +/- 34) ng/g wet tissue, low dosage (155 +/- 95) ng/g wet tissue and high dosage groups (128 +/- 101) ng/g wet tissue.</p><p><b>CONCLUSION</b>This study underlines the importance of alterations in the monoamine neurotransmitters system as a possible causative mechanism behind the behavioural and functional changes produced by acrylonitrile.</p>