Tau hyperphosphorylation is a main cause of neuronal loss in Alzheimer＇s disease, which can be caused by many factors, including oxidative stress. The multifunctional protein p62, which exists in neurofibrillary tang...Tau hyperphosphorylation is a main cause of neuronal loss in Alzheimer＇s disease, which can be caused by many factors, including oxidative stress. The multifunctional protein p62, which exists in neurofibrillary tangles and causes aggregation of hyperphosphorylated tau, not only serves as a receptor in selective autophagy, but also regulates oxidative stress. However, whether p62 participates in oxidative stress-induced tau hyperphosphorylation remains unclear. In this study, we produced an Alzheimer＇s disease rat model by injecting 13-amyloid protein into the hippocampus and ^-galactose intraperitoneally. Hematoxylin-eosin staining was used for morphological analysis of brain tissue, and western blotting, immunohistochemistry and reverse transcription-PCR were employed to study p62 and autophagy related proteins, antioxidant defense system kelch-like ECH-associated protein 1-NF-E2-related factor 2 related proteins and hyperphosphorylated tau, respectively. The number of neurons in the brain decreased in Aizheimer＇s disease rats, and the autophagy related proteins Atg12-Atg5, microtubule-associated protein 1 light chain 3-phosphatidylethanolamine and Beclinl increased significantly, while p62 expression reduced. Expression of kelch-like ECH-associated protein 1 increased, NF-E2-related factor 2 protein and the downstream gene products of glutamate cysteine ligase catalytic subunit and glutamate cysteine ligase modulatory subunit decreased, and hyperphosphorylated tau increased. These findings demonstrate that autophagy levels increased and p62 levels decreased in the brains of Alzheimer＇s disease rats. Moreover, the anti-oxidative capability of the NF-E2-related factor 2-antioxidant response element pathway was decreased, which may be the cause of tau hyperphosphorylation in Alzheimer＇s disease brain tissue and the subsequent structural and functional damage to neurons.展开更多
Metabolizing enzymes play important roles in the detoxification of various pollutants in aquatic organisms, thereby they can also be used to provide early-warning signals of environmental risks. Real-time quantitative...Metabolizing enzymes play important roles in the detoxification of various pollutants in aquatic organisms, thereby they can also be used to provide early-warning signals of environmental risks. Real-time quantitative reverse-transcription polymerase chain reaction assays were developed to quantify cytochrome P450 1A （CYP1A）, superoxide dismutase （SOD）, glutathione peroxidase （GPx）, catalase （CAT）, and glutathione-S-transferase （GST） in crucian carp （Carassius auratus）. The methods were then used to detect the respective mRNA expression levels in liver tissue in wild crucian carp from the Hun River, North China. CYP1A mRNA expression was significantly up-regulated in fish from stations $5, $6, and $8 （p 〈 0.05）. SOD mRNA expression was significantly down-regulated in downstream areas relative to fish from upstream sites （p 〈 0.05）; GPx and CAT mRNA expression levels were also down-regulated at $9 （p 〈 0.05）. In contrast, GST mRNA expression showed no obvious change between fish collected from up- or downstream areas of the river. Finally, an integrated biomarker response was used to evaluate the integrated impact of pollutants in the Hun River and allow better comprehension of the real toxicological risk of these investigated sites.展开更多
Sulfated rhamnose polysaccharide(SRP)derived from Enteromorpha prolifera is a metal-ion chelating agent that could potentially be used to treat diabetes.The aim of our study was to determine the effect of a variant of...Sulfated rhamnose polysaccharide(SRP)derived from Enteromorpha prolifera is a metal-ion chelating agent that could potentially be used to treat diabetes.The aim of our study was to determine the effect of a variant of SRP on DIABETES.First,we synthesized and characterized SRPE-3 chromium(III)[SRPE-3-Cr(III)]complex using an enzymatic method.The maximum chelation rate was 18.2%under optimal chelating conditions of pH 6.0,time 4 h,and temperature 60°C.Fourier transform infrared spectroscopy results showed important sites for Cr(III)-binding were O–H and C=O groups.We then studied the hypolipidemic effects of SRPE-3-Cr(III)on type 2 diabetes mellitus(T2DM)induced by a high-fat,high-sucrose diet(HFSD).Decreased blood glucose content,body fat ratio,serum TG,TC,LDL-C,and increased serum HDL-C were observed after treatment with SRPE-3-Cr(III).In addition,SRPE-3-Cr(III)significantly reduced leptin,resistin,and TNF-αlevels,and increased adiponectin contents relative to T2DM.Histopathology results also showed that SRPE-3-Cr(III)could alleviate the HFSD-lesioned tissues.SRPE-3-Cr(III)also improved lipid metabolism via a reduction in aspartate aminotransferase,alanine aminotransferase,fatty acid synthase,and acetyl-CoA carboxylase activities in the liver.SRPE-3-Cr(III)at low doses exhibited better lipid-lowering activities,hence,could be considered to be a novel compound to treat hyperlipidemia and also act as an anti-diabetic agent.展开更多
文摘Tau hyperphosphorylation is a main cause of neuronal loss in Alzheimer＇s disease, which can be caused by many factors, including oxidative stress. The multifunctional protein p62, which exists in neurofibrillary tangles and causes aggregation of hyperphosphorylated tau, not only serves as a receptor in selective autophagy, but also regulates oxidative stress. However, whether p62 participates in oxidative stress-induced tau hyperphosphorylation remains unclear. In this study, we produced an Alzheimer＇s disease rat model by injecting 13-amyloid protein into the hippocampus and ^-galactose intraperitoneally. Hematoxylin-eosin staining was used for morphological analysis of brain tissue, and western blotting, immunohistochemistry and reverse transcription-PCR were employed to study p62 and autophagy related proteins, antioxidant defense system kelch-like ECH-associated protein 1-NF-E2-related factor 2 related proteins and hyperphosphorylated tau, respectively. The number of neurons in the brain decreased in Aizheimer＇s disease rats, and the autophagy related proteins Atg12-Atg5, microtubule-associated protein 1 light chain 3-phosphatidylethanolamine and Beclinl increased significantly, while p62 expression reduced. Expression of kelch-like ECH-associated protein 1 increased, NF-E2-related factor 2 protein and the downstream gene products of glutamate cysteine ligase catalytic subunit and glutamate cysteine ligase modulatory subunit decreased, and hyperphosphorylated tau increased. These findings demonstrate that autophagy levels increased and p62 levels decreased in the brains of Alzheimer＇s disease rats. Moreover, the anti-oxidative capability of the NF-E2-related factor 2-antioxidant response element pathway was decreased, which may be the cause of tau hyperphosphorylation in Alzheimer＇s disease brain tissue and the subsequent structural and functional damage to neurons.
基金supported by the Water Pollution Control and Management(No.2009ZX07528)
文摘Metabolizing enzymes play important roles in the detoxification of various pollutants in aquatic organisms, thereby they can also be used to provide early-warning signals of environmental risks. Real-time quantitative reverse-transcription polymerase chain reaction assays were developed to quantify cytochrome P450 1A （CYP1A）, superoxide dismutase （SOD）, glutathione peroxidase （GPx）, catalase （CAT）, and glutathione-S-transferase （GST） in crucian carp （Carassius auratus）. The methods were then used to detect the respective mRNA expression levels in liver tissue in wild crucian carp from the Hun River, North China. CYP1A mRNA expression was significantly up-regulated in fish from stations $5, $6, and $8 （p 〈 0.05）. SOD mRNA expression was significantly down-regulated in downstream areas relative to fish from upstream sites （p 〈 0.05）; GPx and CAT mRNA expression levels were also down-regulated at $9 （p 〈 0.05）. In contrast, GST mRNA expression showed no obvious change between fish collected from up- or downstream areas of the river. Finally, an integrated biomarker response was used to evaluate the integrated impact of pollutants in the Hun River and allow better comprehension of the real toxicological risk of these investigated sites.
基金funded by the Innovation Capability Improvement Project of Shandong(2021TSGC1298)the Qingdao Science and Technology Project(2022).
文摘Sulfated rhamnose polysaccharide(SRP)derived from Enteromorpha prolifera is a metal-ion chelating agent that could potentially be used to treat diabetes.The aim of our study was to determine the effect of a variant of SRP on DIABETES.First,we synthesized and characterized SRPE-3 chromium(III)[SRPE-3-Cr(III)]complex using an enzymatic method.The maximum chelation rate was 18.2%under optimal chelating conditions of pH 6.0,time 4 h,and temperature 60°C.Fourier transform infrared spectroscopy results showed important sites for Cr(III)-binding were O–H and C=O groups.We then studied the hypolipidemic effects of SRPE-3-Cr(III)on type 2 diabetes mellitus(T2DM)induced by a high-fat,high-sucrose diet(HFSD).Decreased blood glucose content,body fat ratio,serum TG,TC,LDL-C,and increased serum HDL-C were observed after treatment with SRPE-3-Cr(III).In addition,SRPE-3-Cr(III)significantly reduced leptin,resistin,and TNF-αlevels,and increased adiponectin contents relative to T2DM.Histopathology results also showed that SRPE-3-Cr(III)could alleviate the HFSD-lesioned tissues.SRPE-3-Cr(III)also improved lipid metabolism via a reduction in aspartate aminotransferase,alanine aminotransferase,fatty acid synthase,and acetyl-CoA carboxylase activities in the liver.SRPE-3-Cr(III)at low doses exhibited better lipid-lowering activities,hence,could be considered to be a novel compound to treat hyperlipidemia and also act as an anti-diabetic agent.
