本文選題：秀麗新桿線蟲 + 肌管素��； 參考：《吉林大學》2011年博士論文

【摘要】：第一篇:蛋白質磷酸酶是細胞信號轉導過程中發(fā)揮至關重要作用的一類蛋白質,其家族成員與多種人類疾病的發(fā)生、發(fā)展密切相關。肌管素磷酸酶亞家族(Myotubularins,MTMs)隸屬于蛋白質磷酸酶超家族,該亞家族成員以磷酸肌醇(phosphatidylinositol, PI)作為其特異性的催化底物進行去磷酸化。人類的肌管素磷酸酶機組成員MTM-1突變可導致X-連鎖的肌小管性肌病,MTMR2和MTMR13的突變可導致腓骨肌萎縮癥,但肌管素磷酸酶引發(fā)其相關疾病的機理尚不清楚。本研究選用秀麗新桿線蟲作為生物模型,利用RNA干擾的方法及相關的突變體對線蟲肌管素磷酸酶成員ceMTM3、ceMTM6和ceMTM9進行了研究。 我們的研究結果表明,ceMTM3能夠影響線蟲體內肌纖維的保持并對線蟲體內自吞噬的發(fā)生起著負調控的作用。利用RNA干擾的方法降低線蟲體內ceMTM3的表達量可加速線蟲在衰老的過程中肌纖維的流失,使線蟲的肌肉細胞發(fā)生萎縮變小,并在線蟲體內肌肉細胞及其他組織中引起自吞噬水平顯著升高。在自吞噬水平升高后,ceMTM3表達量的降低還導致了細胞體內溶酶體水平升高以及細胞壞死。Atg-18在線蟲體內發(fā)生自吞噬的過程中能夠與PI3P相結合并對自吞噬小體的形成起重要的調節(jié)作用,atg-18突變型線蟲自身存在運動障礙,并且相比野生型線蟲其肌肉細胞內肌纖維排列混亂。當對atg-18突變型線蟲進行ceMTM3干擾后,我們發(fā)現(xiàn)在atg-18突變型線蟲的體內降低ceMTM3的表達量并未使該突變株線蟲體內的肌纖維排列進一步惡化。這說明ceMTM3對線蟲肌纖維保持的調節(jié)作用是通過其對自吞噬的調控來實現(xiàn)的。本研究為揭示人類肌纖維保持的調節(jié)機制及治療人骨骼肌減少癥提供了依據(jù)和基礎。此外,我們還對線蟲體內另外兩名肌管素成員ceMTM6和ceMTM9的生物學功能進行了研究。研究結果表明,mtm-6突變型線蟲相比野生型體長較短、存在運動障礙。在發(fā)育的過程中進行肌肉染色的結果表明,相比野生型,mtm-6突變型的線蟲肌細胞間隙較大且肌細胞較小,此外,約20% mtm-6突變型線蟲的生殖腺在發(fā)育的過程中延伸方向發(fā)生了錯誤。整合素在細胞表面的分布和表達對細胞之間的粘附和細胞遷移有重要的調節(jié)作用。我們初步的研究結果表明,mtm-6能夠影響線蟲體內神經細胞DTCs表面整合素INA-1的表達和分布,而這極有可能是ceMTM6影響線蟲肌肉細胞和生殖腺發(fā)育的原因之一。ceMTM9不具備催化活性中心,之前的研究結果表明,ceMTM9可與ceMTM6結合形成復合體共同發(fā)揮作用。本研究的結果表明,mtm-9突變型線蟲可使線蟲發(fā)育遲緩、體長較小、產卵數(shù)明顯降低Bagged Worm比率顯著升高并且壽命縮短。對mtm-9突變型線蟲進行ceMTM3干擾的結果表明,ceMTM9和ceMTM3之間可能存在著相互代償?shù)淖饔谩?第二篇:酒精飲料是人類日常生活中必不可少的飲品。長期酗酒對人體有較大傷害,但近期的研究結果表明,長期適量飲酒可降低人類某些疾病的發(fā)病率,因此飲酒的利弊仍存在爭議。本研究以秀麗新桿線蟲作為模型,研究了不同濃度的酒精長期刺激線蟲各種生命活動的影響。研究結果表明,長期高濃度的酒精刺激(≥4%)使線蟲壽命縮短、產卵數(shù)減少、運動能力減弱。有趣的是,長期低濃度的酒精刺激(1-2%)可使線蟲壽命延長。盡管產卵數(shù)有所減少,但長期2%濃度的酒精刺激可使線蟲的壽命延長約2.76天,延長率達14.53%,并且伴隨著運動的衰老程度減緩。研究發(fā)現(xiàn),這種作用與線蟲體內的類胰島素信號通路以及轉錄因子Sir-2.1密切相關。相比未刺激的對照組,無論從卵、幼蟲還是成蟲開始2%酒精刺激都可使線蟲壽命顯著延長。本研究證明了線蟲是研究長期酒精刺激的優(yōu)秀模型并且長期少量的酒精刺激能夠對機體產生積極的作用。本研究為進一步研究不同劑量酒精長期刺激對人類的生理功能的影響以及所引發(fā)的與之相關的分子機制奠定了基礎。
[Abstract]:Protein phosphatase is a kind of protein that plays a vital role in cell signal transduction. Its family members are closely related to the development of a variety of human diseases. The Myotubularins (MTMs) belongs to the protein phosphatase superfamily, and the member of the subfamily is inositol phosphate (phosphatidylino). Sitol, PI) dephosphorylation as its specific catalytic substrate. Human myotin phosphatase unit MTM-1 mutation can lead to X- linked myomatosis. Mutations in MTMR2 and MTMR13 can lead to fibula muscular dystrophy, but the mechanism of myotin phosphatase that causes its related diseases is not clear. As a biological model, the ceMTM3, ceMTM6 and ceMTM9 of the nematode myotube phosphatase were studied by means of RNA interference and related mutants.
Our results showed that ceMTM3 could affect the retention of the muscle fibers in the nematode and negatively regulated the self phagocytosis of the nematode in the nematode. The reduction of the ceMTM3 expression in the nematode by RNA interference could accelerate the loss of muscle fibers in the aging process, and reduce the atrophy of the nematode muscle cells. The level of autophagy increased significantly in the muscle cells and other tissues in the body of the worm. The decrease of the expression of ceMTM3 also resulted in the increase of the lysosome level in the cells and the formation of the autophagy of the autophagocytic body in the process of the autophagy of the cell necrosis.Atg-18 in the body of the cells after the increase of autophagy. Important regulation, atg-18 mutant nematodes themselves have dyskinesia, and the muscle fibers in the muscle cells of the wild type nematode are confused. When ceMTM3 interference is done to atg-18 mutant nematodes, we found that the reduction of ceMTM3 in the body of the atg-18 mutant nematode did not make the muscle fiber in the mutant nematode. This shows that the regulation of ceMTM3 on the retention of nematode muscle fibers is achieved through its regulation of autophagy. This study provides a basis and basis for revealing the regulatory mechanism of human muscle fiber retention and the treatment of human skeletal myocytosis. In addition, we also have two other myosin members, ceMTM6 and C, in line worms. The biological function of eMTM9 was studied. The results showed that the mtm-6 mutated nematode was shorter than the wild type, and there was a dyskinesia. The results of muscle staining during development showed that the myocytes of the nematode of the mtm-6 mutant were larger and smaller than the wild type. In addition, about 20% mtm-6 mutant nematodes were born. The distribution and expression of integrin on cell surface have important regulatory effect on cell adhesion and cell migration. Our preliminary results show that mtm-6 can affect the expression and distribution of DTCs surface integrin INA-1 in the nerve cells of the nematode, and this is very likely. It is one of the reasons that ceMTM6 affects the development of the nematode muscle cells and the reproductive glands of the nematode..ceMTM9 does not have the catalytic activity center. The previous research results show that ceMTM9 can combine with ceMTM6 to form complex complex. The results of this study show that the mtm-9 mutant nematode can make the nematode grow slow, the body length is smaller, and the number of spawns obviously reduces the Bagged W. The ORM ratio was significantly higher and the life span was shortened. The results of ceMTM3 interference to the mtm-9 mutant nematode showed that there might be a mutual compensatory effect between ceMTM9 and ceMTM3.
Second: alcohol is an essential drink in human daily life. Long term alcohol abuse is very harmful to people. But recent research shows that long term alcohol consumption can reduce the incidence of certain diseases in human beings. Therefore, the advantages and disadvantages of drinking are still controversial. The effects of alcohol on the life of the nematodes for a long time. The results showed that long term high concentration of alcohol (> 4%) shortened the life span of the nematode, reduced the number of spawns, and weakened the exercise ability. Interestingly, the long term low concentration of alcohol stimulation (1-2%) could prolong the life of the nematode. Although the number of eggs was reduced, the long-term 2% concentration of alcohol was stimulated. The life span of the nematode can be extended by about 2.76 days, with an extension of 14.53%, and the slowing of the aging of the movement. The study found that this effect is closely related to the insulin like signaling pathway and the transcription factor Sir-2.1 in the nematode. Compared to the unstimulated control group, the 2% alcohol stimulation from the egg, the larva and the adult can make the nematode in the nematode. This study demonstrated that the nematode is an excellent model for long-term alcohol stimulation and a long amount of alcohol stimulation can have a positive effect on the body. This study provides a further study of the effects of the long-term stimulation of alcohol on the physiological functions of human beings and the related molecular mechanisms. Basics.

【學位授予單位】：吉林大學
【學位級別】：博士
【學位授予年份】：2011
【分類號】：R341

【共引文獻】

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