Dissertation > Excellent graduate degree dissertation topics show

MPP~+-induced Autophagic Stress in Cellular Injury and Its Regulation Mechanisms

Author: ShiJiJun
Tutor: LiuChunFeng
School: Suzhou University
Course: Neurology
Keywords: Autophagy Autophagic stress α-synuclein MPP ~ (1 - methyl-4 - phenylpyridinium ion) Parkinson's disease Dynein
CLC: R736.6
Type: Master's thesis
Year: 2010
Downloads: 169
Quote: 0
Read: Download Dissertation

Abstract


The first part of the MPP ~ of MPP ~ autophagy induced stress in pheochromocytoma (PC12) cell damage induced PC12 cells to explore the purpose of self-macrophage stress and α-synuclein autophagic mechanism remove barriers, MPP ~ may lead to α-synuclein (α-synuclein) autophagic remove barriers to its abnormal accumulation mechanism and the relationship between the different levels of self-macrophage stress level of cell damage. Our group has successfully constructed over-expressing the human A30P pathogenic mutation of α-synuclein in PC12 cells model MPP ~ treated cells 24h after dimethylthiazol-salt (MTT) the detection cell viability, Western blot detection α-synuclein, micro tube associated protein 1 light chain 3 - Ⅱ (LC3-Ⅱ) and power proteins in the protein level of expression of the change and MDC staining and immune fluorescence labeled observe autophagy level of change and α-synuclein, LC3-Ⅱ and lysosomal-associated membrane protein -1 (LAMP-1) in the intracellular co-localization. At the same time, observed after treatment with different concentrations of MPP ~ the different autophagic stress levels of α-synuclein, LC3 and dynein expression at the protein level, and apoptosis. MPP ~ the viability of cells after treatment decreased significantly; the PC12 MPP ~ group (PC12 group: 0.200 ± 0.084; the A30P groups: 0.758 ± 0.085) compared with the untreated group (0.660 ± 0.072, P lt; 0.01) and A30P MPP to group (1.707 ± 0.400, P lt; 0.001) the expression of α-synuclein increased; LC3-II protein expression levels and the average number of autophagic vacuoles were increased, and the difference was statistically significant;, MPP to treatment of α- synuclein LC3-Ⅱ fluorescence signal and its colocalization increase, increase the the lysosomal fluorescence signal of the LAMP-1 marker, LC3-Ⅱ labeled autophagosome degree of co-localization was reduced. In addition, different concentrations of MPP ~ induced autophagy stress on PC12 cells have different effects on MPP ~ concentration increased autophagy stress levels were significantly higher increase in apoptotic cells, easy aggregation of α-synuclein protein increased expression mediated reduced from phages fusion with lysosomes key motor proteins - dynein expression. Conclusion MPP ~ autophagy induced stress impaired dynein autophagic remove barriers caused by α-synuclein is closely related to that dynein dysfunction plays an important role in cell damage, dynein α-synuclein self macrophages sexual degradation of the key targets of the regulation. The second part of the dynein: formation of autophagy stress, a key regulator of the target Objective To investigate the α-synuclein dynein-mediated degradation obstacles in the formation of autophagic stress effect and its mechanism, and provide new therapeutic strategies for the prevention and treatment of PD and-control targets. Constructed using siRNA knock-down of dynein cell model, then using immunocytochemistry and Western blot to observe changes in the expression of α-synuclein and autophagy levels, transmission electron microscopy and cell ultrastructural changes and autophagy morphological changes; intraperitoneal injection constructed rotenone-induced PD rat model, using the Western blot method rotenone-induced PD rat striatal dynein, α-synuclein and autophagy changes were observed and analyzed. Results of by siRNA technology interference power protein's function will cause of α-synuclein obvious aggregation (P lt; 0.01); rotenone treatment dynein expression decreased (P lt; 0.01), the expression of α-synuclein increased and aggregation (P lt; 0.01 increased), LC3-Ⅱ expression (since phages increase) (P lt; 0.05), of mTOR phosphorylation level decreased (ie inhibition of mTOR raised since macrophages) (P lt; 0.05), which showed that rotenone treatment caused power protein function obstacles The cause of α-synuclein aggregation increase as well as the increase in autophagosome formation (ie the autophagy stress level increased), mTOR involved in this process of autophagy induced. Conclusion dynein-mediated autophagic degradation of α-synuclein dysfunction mediated accumulation of α-synuclein aggregation and autophagy by autophagy dynein regulation of α-synuclein degradation potential adjustment in PD prevention targets.

Related Dissertations

  1. Effect of Different Glucose Concentrations on Autophagy in Neonatal Rat Cardiomyocyte Culture,R542.2
  2. Apoptosis Mechanisms Research in Interfering TIGAR Gene and Epirubicin Treatmnet in Hepatic Carcinoma Cells,R735.7
  3. The Effect of Gefitinib in Radiosensitization Through Autophagy Regulation in Human Non-small-cell Lung Cancer A549 Cell Line,R734.2
  4. Amiloride Is Protective in PC12 Cells Via Autophagy Pathway,R329
  5. The Effects of ER Stress on Cell Toxicity and Htt Levels in the Stable PC12 Cells Expressing Htt586,R363
  6. Intervention and Mechanisms of E-64d on Developmental Seizure-induced Cognitive Deficit,R720.597
  7. Effects of Lysosomal Enzyme Inhibitor on Recurrent Neonatal Seizure Induced Acute and Long-term Gene Expression and Behavioral Changes,R720.597
  8. The Effects of Autophagy on Cardiomyocytes Viability and Mitochondrial Membrane Potential in Sepsis,R459.7
  9. Autophagy marker protein LC3 lifetime studies in rats,R743
  10. Suppression of Autophagy-related Gene Causes Locomotive Defects in Drosophila,R741
  11. The Relationship between Phosphorylation of ataxin-3 and Autophagy,R744
  12. Power Frequency Magnetic Fields Induce Autophagy in the Chinese Hamster Lung Cells,R363
  13. Studies on the Cytoprotective Effect of Glycine and Its Mechanism,R965
  14. Detecting the Expression of the Autophagy-related Gene in the Nude Mouse Model of Human Lung Cancer Cell Line A549,R734.2
  15. Expression of Beclin-1 mRNA and Protein in Ovarian Endometriosis,R711.71
  16. The Expression of Osteopontin and Autophagy-related Genes in Abdominal Aortic Aneurysm and the Molecular Mechanism of Osteopontin-induced Autophagy of Smooth Muscle Cells,R543
  17. Melatonin Protects N2a Against Ischemia/Reperfusion Injury Through Autophagy Enhancement,R363
  18. Scavenger Receptor A Pathway Inhibits Endoplasmic Reticulum Stress-induced Autophagy in Macrophage,R730.2
  19. Study of Mechanisms of Jurkat and Raji Cell Death Induced by Resveratrol,R733.1
  20. The Changes and Significance of Autophagy after Subarachnoid Hemorrhage in Rats,R651.1
  21. Simulated Microgravity Induces Human Umbilical Vein Endothelial Cells Autophagy,R85

CLC: > Medicine, health > Oncology > Internal endocrine tumors > Adrenal tumors
© 2012 www.DissertationTopic.Net  Mobile