- 學位論文
外界環境的刺激對於第十型葡萄糖轉運蛋白位在粒線體影響之研究
Environmental stimulations effect GLUT10 targeting to mitochondria in aortic smooth muscle cell
若您是本文的作者，可授權文章由華藝線上圖書館中協助推廣。
摘要
第十型葡萄糖轉運蛋白(Glucose transporter 10, GLUT10)屬於第三類型葡萄糖轉運蛋白家族，由SLC2A10基因轉譯而成。過去文獻已經證實當GLUT10基因突變時，會導致主動脈血管扭曲疾病(Arterial tortuosity syndrome, ATS)。先前實驗室已證實GLUT10在分化脂肪細胞中受到胰島素(Insulin)的刺激下，會由高基氏體(Golgi)轉移至粒線體(Mitochondria)；在主動脈平滑肌細胞，不論有沒有受到胰島素的刺激皆會位在粒線體。此外也證實GLUT10位在粒線體可做為脫氫抗壞血酸(dehydroascorbic acid, DHA)運送子，可以避免細胞免受於氧化壓力的破壞，然而氧化壓力與心血管疾病的產生也是息息相關，因此也說明了GLUT10在粒線體上扮演著重要的角色。在此篇研究中，我們想瞭解GLUT10位在粒線體的比例與細胞受到外在環境刺激的關聯，我們透過對主動脈平滑肌細胞給予不同外在刺激條件下，其中包括細胞形態不同、培養液葡萄糖濃度、H2O2處理。我們發現細胞在處理H2O2情況下，細胞內除了活性氧化壓力增加外，粒線體形態與膜電位皆有受到影響，並且發現GLUT10位在粒線體的比例有所增加。此篇論文實驗結果說明了GLUT10位在粒線體的比例是會受到外界刺激的影響而改變的，同時也說明了GLUT10與氧化壓力誘發疾病的關聯性。
並列摘要
Facilitative glucose transporter member 10 (GLUT10) protein, also known SLC2A10 gene, belong to the class III GLUT family. Recent studies have been reported SLC2A10 gene mutation caused arterial tortuosity syndrome (ATS). Our laboratory previously demonstrated that GLUT10 is localized to the mitochondria and mediated dehydroascorbic acid (DHA) transport into mitochondria to reduced reactive oxygen species (ROS) production. However the molecular mechanisms of GLUT10 targeting mitochondria are still obscure. We hypothesis that GLUT10 targeting to mitochondria were regulated by external-stimulus in the A10 cell. Here, we used confocal image data and Imaris software further analysis the levels of GLUT10 spot pattern percentage, which co-localized with mitochondria, were increased upon long-term H2O2 treatment but not glucose and insulin stimulation. These results indirectly revealed the functions of GLUT10 that reduced mitochondrial ROS production through increased levels of mitochondria targeting. It is concluded that GLUT10 has response to ROS and increase the mitochondria targeting percentage upon long-term H2O2 stimulation.
參考文獻
Son, Y., Cheong, Y.K., Kim, N.H., Chung, H.T., Kang, D.G., and Pae, H.O. (2011). Mitogen-Activated Protein Kinases and Reactive Oxygen Species: How Can ROS Activate MAPK Pathways? J. Signal Transduct. 2011, 792639.
Ades, L.C., Knight, W.B., Byard, R.W., Bateman, J.F., Esquivel, J.A., Mee, R.B., Haan, E.A., and Milewicz, D.M. (1996). Clinicopathologic findings in congenital aneurysms of the great vessels. Am. J. Med. Genet. 66, 289-299.
Bereiter-Hahn, J.V., M. (1994 ). Dynamics of Mitochondria in Living Cells:Shape Changes, Dislocations, Fusion, and Fission of Mitochondria. Microsc. Res. Tech. 27, 198-219.
Beuren, A.J., Hort, W., Kalbfleisch, H., Muller, H., and Stoermer, J. (1969). Dysplasia of the systemic and pulmonary arterial system with tortuosity and lengthening of the arteries. A new entity, diagnosed during life, and leading to coronary death in early childhood. Circulation 39, 109-115.
Cheng, C.H., Kikuchi, T., Chen, Y.H., Sabbagha, N.G., Lee, Y.C., Pan, H.J., Chang, C., and Chen, Y.T. (2009). Mutations in the SLC2A10 gene cause arterial abnormalities in mice. Cardiovasc. Res. 81, 381-388.