Limits...
Effect of p62 on tau hyperphosphorylation in a rat model of Alzheimer's disease.

Zheng X, Wang W, Liu R, Huang H, Zhang R, Sun L - Neural Regen Res (2012)

Bottom Line: However, whether p62 participates in oxidative stress-induced tau hyperphosphorylation remains unclear.The number of neurons in the brain decreased in Alzheimer's disease rats, and the autophagy related proteins Atg12-Atg5, microtubule-associated protein 1 light chain 3-phosphatidylethanolamine and Beclin1 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cytobiology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, Jilin Province, China.

ABSTRACT
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 β-amyloid protein into the hippocampus and β-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 Alzheimer's disease rats, and the autophagy related proteins Atg12-Atg5, microtubule-associated protein 1 light chain 3-phosphatidylethanolamine and Beclin1 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.

No MeSH data available.


Related in: MedlinePlus

Changes in autophagy-associated proteins and p62 expression in the rat cerebral cortex and hippocampus.Western blot analysis (A) and quantification of the expression of Atg12-Atg5, LC3-II, beclin1 and p62 in the cerebral cortex of the saline and AD model group as compared with the control (CON) group (adjusted as 1.0) (B–E).Western blot analysis (F) and quantification of the expression of Atg12-Atg5, LC3-II, beclin1, and p62 in the hippocampus as compared with the control group (adjusted as 1.0) (G–J).β-actin was used as an internal standard. The assay was performed three times and data were expressed as mean ± SD. aP < 0.05, bP < 0.01, vs. the control group (one-way analysis of variance followed by Dunnett's t-test).Atg: Autophagy-related genes; LC3: microtubule-associated protein 1 light chain 3; AD: Alzheimer's disease.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4308800&req=5

Figure 2: Changes in autophagy-associated proteins and p62 expression in the rat cerebral cortex and hippocampus.Western blot analysis (A) and quantification of the expression of Atg12-Atg5, LC3-II, beclin1 and p62 in the cerebral cortex of the saline and AD model group as compared with the control (CON) group (adjusted as 1.0) (B–E).Western blot analysis (F) and quantification of the expression of Atg12-Atg5, LC3-II, beclin1, and p62 in the hippocampus as compared with the control group (adjusted as 1.0) (G–J).β-actin was used as an internal standard. The assay was performed three times and data were expressed as mean ± SD. aP < 0.05, bP < 0.01, vs. the control group (one-way analysis of variance followed by Dunnett's t-test).Atg: Autophagy-related genes; LC3: microtubule-associated protein 1 light chain 3; AD: Alzheimer's disease.

Mentions: The border between the nucleus and cytoplasm was indistinct, neuronal layering was reduced, the number of neurons in the forebrain cortex in the AD model group was reduced, and pyknosis and hyperchromasia were observed.


Effect of p62 on tau hyperphosphorylation in a rat model of Alzheimer's disease.

Zheng X, Wang W, Liu R, Huang H, Zhang R, Sun L - Neural Regen Res (2012)

Changes in autophagy-associated proteins and p62 expression in the rat cerebral cortex and hippocampus.Western blot analysis (A) and quantification of the expression of Atg12-Atg5, LC3-II, beclin1 and p62 in the cerebral cortex of the saline and AD model group as compared with the control (CON) group (adjusted as 1.0) (B–E).Western blot analysis (F) and quantification of the expression of Atg12-Atg5, LC3-II, beclin1, and p62 in the hippocampus as compared with the control group (adjusted as 1.0) (G–J).β-actin was used as an internal standard. The assay was performed three times and data were expressed as mean ± SD. aP < 0.05, bP < 0.01, vs. the control group (one-way analysis of variance followed by Dunnett's t-test).Atg: Autophagy-related genes; LC3: microtubule-associated protein 1 light chain 3; AD: Alzheimer's disease.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4308800&req=5

Figure 2: Changes in autophagy-associated proteins and p62 expression in the rat cerebral cortex and hippocampus.Western blot analysis (A) and quantification of the expression of Atg12-Atg5, LC3-II, beclin1 and p62 in the cerebral cortex of the saline and AD model group as compared with the control (CON) group (adjusted as 1.0) (B–E).Western blot analysis (F) and quantification of the expression of Atg12-Atg5, LC3-II, beclin1, and p62 in the hippocampus as compared with the control group (adjusted as 1.0) (G–J).β-actin was used as an internal standard. The assay was performed three times and data were expressed as mean ± SD. aP < 0.05, bP < 0.01, vs. the control group (one-way analysis of variance followed by Dunnett's t-test).Atg: Autophagy-related genes; LC3: microtubule-associated protein 1 light chain 3; AD: Alzheimer's disease.
Mentions: The border between the nucleus and cytoplasm was indistinct, neuronal layering was reduced, the number of neurons in the forebrain cortex in the AD model group was reduced, and pyknosis and hyperchromasia were observed.

Bottom Line: However, whether p62 participates in oxidative stress-induced tau hyperphosphorylation remains unclear.The number of neurons in the brain decreased in Alzheimer's disease rats, and the autophagy related proteins Atg12-Atg5, microtubule-associated protein 1 light chain 3-phosphatidylethanolamine and Beclin1 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cytobiology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, Jilin Province, China.

ABSTRACT
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 β-amyloid protein into the hippocampus and β-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 Alzheimer's disease rats, and the autophagy related proteins Atg12-Atg5, microtubule-associated protein 1 light chain 3-phosphatidylethanolamine and Beclin1 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.

No MeSH data available.


Related in: MedlinePlus