Research advances in selective adaptor protein autophagy of p62/sequestosome-1 / 中国药理学与毒理学杂志

p62/sequestosome-1(SQSTM1)is an important selective autophagy adaptor protein, which contains six functional regions:ubiquitin-binding domain,Keap1 interacting region,LC3 interaction region,tumor necrosis factor receptor-associated factor 6 binding domain,Phox and Bem1p and ZZ-type zinc finger domain. p62/SQSTM1 plays an important role in the removal of ubiquitin proteins. It also regulates the signaling pathway of nuclear factor erythroid 2 related factor 2-antioxidant respose element, NF-κB and the caspase-8 mediated apoptosis. The abnormal expression of p62/SQSTM 8 is closely related to neurodegenerative diseases (such as Huntington disease,Alzheimer disease,Parkinson disease),cancer,infective diseases,genetic diseases and chronic diseases. So far many researchers have shed light on the structure function and mechanism of p62/SQSTM1. This paper reviews the role of p62/SQSTM1 in the metabolism of proteins,the regulation of multiple signaling pathways and in the occurrence of diseases in order to provide a new theoretical basis for the treatment of autophagy targets.

Changes in the expression and phosphorylation state of autophagy-related protein ATG4 in nervous tissues of hens treated with tri-ortho-cresyl phosphate / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the changes in the levels of authophagy-related proteins ATG4A and p-ATG4A in nervous tissue after treated with tri-ortho-cresyl phosphate and explore the possible pathogenesis of OPIDN.</p><p><b>METHODS</b>In the first experiment, thirty hens were randomly divided into control group and 1 d, 5 d, 10 d and 21d treated groups, hens in treated groups were treated with TOCP by gavage at a single dosage of 600 mg/kg. In the second experiment, other thirty hens were also randomly divided into control group and 1 d, 5 d, 10 d and 21 d treated groups, hens in treated group were pretreated with PMSF by subcutaneous at a single dosage of 90 mg/kg. 24 h later, hens in intervention group was treated with TOCP by gavage at a single dosage of 600 mg/kg. The hens were killed at the corresponding time points, and collected their tibial nerves. The levels of ATG4A and p-ATG4A were measured by immunoblotting.</p><p><b>RESULTS</b>compared with the control group, the levels of ATG4A decreased by36%, 43.7% and 41% at 1d, 5d and 10d in the intoxication groups (P < 0.05), the levels of p-ATG4A decreased by 22.5%, 25%and 21%at 1d, 5d and 10d in the intoxication group (P < 0.05). However, compared with the control group, there is no significant change in the levels of ATG4A and p-ATG4A in PMSF-pretreated groups.</p><p><b>CONCLUSION</b>The intoxication of TOCP influence the levels of autophagy-related proteins ATG4A and p-ATG4A, which might be associated with the inhibition of autophagy activity in neurons of OPIDN.</p>

Changes in expression of motor protein for axonal transport in nerve tissues of carbon disulfide-intoxicated rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the changes in microtubule motor protein expression in the spinal cord and sciatic nerve of rats exposed to carbon disulfide, and to investigate the possible molecular mechanism of changes in axonal transport in carbon disulfide-induced peripheral neuropathy.</p><p><b>METHODS</b>Healthy adult male Wistar rats were randomly divided into one control group and three experimental groups (10 rats per group). The rats in experimental groups were intoxicated by gavage of carbon disulfide at a dose of 200, 400, or 600 mg/kg 6 times a week for 6 consecutive weeks, while the rats in control group were given the same volume of corn oil by gavage. Animals were sacrificed after exposure, with nerve tissue separated. The levels of dynein, dynactin, and kinesin in the spinal cord and sciatic nerve were determined by Western blot.</p><p><b>RESULTS</b>The content of dynein, dynactin, and kinesin in the sciatic nerve decreased significantly under exposure to carbon disulfide. The levels of dynein in the sciatic nerve were reduced by 23.47% and 33.34% at exposure doses of 400 and 600 mg/kg, respectively. The levels of dynactin in the sciatic nerve of the three experimental groups were reduced by 19.91%, 24.23%, and 41.30%, respectively. The level of kinesin was reduced by 25.98%under exposure to 600 mg/kg carbon disulfide. All the differences were statistically significant (P < 0.01). As compared with the control group, the 600 mg/kg group experienced a 28.24% decrease in level of dynactin in the spinal cord (P < 0.01), but no significant change was observed in the level of dynein or kinesin.</p><p><b>CONCLUSION</b>Carbon disulfide has an impact on microtubule motor protein expression in nerve tissues, which might be involved in the development of carbon disulfide-induced peripheral neuropathy.</p>

Effects of Single High Dose Intake of Ethanol on the Liver of Mice / 环境与健康杂志

Objective To investigate the liver damage caused by single high-dose intake of ethanol in mice. Methods Twenty-four male Kunming mice were randomized into 2 groups. The mice in ethanol group were treated with single dose of ethanol (50%,V/V,12 ml/kg),while the control mice received distilled water. The serum biochemical indices were determined 16 h after ethanol exposure. The hepatic triglyceride (TG) and free fatty acid (FFA) levels and the histological changes were examined to evaluate the fat accumulation,while the Ca2+-induced mitochondrial permeability transition (MPT) was detected for the mitochondrial function assay. The liver and mitochondrial malondialdehyde (MDA) and glutathione (GSH) levels were determined to assess the lipid peroxidation level. The activities and the protein expression of the CYP2E1,1A2,3A were determined. Results Slow response,ataxia and righting reflex disappearance were gradually emerged,which disappeared at about 3 h later. Compared with the control group,the liver index,the serum ALT and AST activities,the hepatic TG,FFA,and MDA levels,and the activity and protein level of the CYP2E1 significantly increased,while the liver GSH level significantly decreased (P0.05). In addition,A540 of ethanol group was higher than that of control group (P

Current Status of Using Vitellogenin as A Biomarker to Screen Endocrine Disruptors / 环境与健康杂志

As harmful effect on human healh and on existence of biological population etiological system may caused by endocrine disruptors, it has become the focus of many studies of public health and environmental protection. This paper briefly summarized the current status of studies on the definition, classification, adverse effects and screening methods of endocrine disruptors, and also reviewed the scientific theory and advantages of vitellogenin that was qualified as a biomarker in screening environmental endocrine disruptors. On the basis of the matters mentioned above, the paper specifically introduced the principle, application, merits and shortcomings for methods for detecting vitellogenin protein and its encoding gene.