探討營養缺乏於微膠細胞所誘導的訊息傳遞

小膠質細胞 (Microglia) 為腦部中樞神經系統的重要細胞之一，與巨噬細胞、樹突細胞一樣具有先天免疫的功能，因此其細胞功能的異常與發炎反應密切相關，也在多種腦部病變的疾病中扮演者重要的角色。過去已有不少研究探討中風缺氧對小膠質細胞功能的影響，但甚少了解腦部血流受阻導致養份供應不足對小膠質細胞的影響。因此本研究是利用HBSS (Hank's Balanced Salt Solution) 處理小膠質細胞株BV-2，藉此模擬缺血性中風發生後細胞處於缺乏營養的狀態，探討在此壓力狀態下對細胞存活及發炎相關訊息傳遞路徑的影響。與一般的細胞培養基不同，HBSS 組成中缺乏胺基酸及維生素，而葡萄糖含量 (1 g/L) 也較一般的細胞培養基 (4.5 g/L) 來的低。綜合本論文的實驗結果，HBSS可以誘導細胞ROS的產生使其走向caspase-independent apoptosis。增加的ROS也會影響各種訊息傳遞路徑。ROS增加會導致AMPK的活化，但會抑制ERK；被HBSS活化的Syk 能正調控ERK的活化，而ROS能夠負調控Syk；HBSS能夠誘導TNF- alpha的產生，但此作用會被NAC、Compound C、R406 所減少。這些結果顯示缺乏營養會誘導多種訊息傳遞路徑而導致小膠質細胞產生TNF- alpha及細胞的死亡。

關鍵字

小膠質細胞；缺血性中風；活性氧化物質；漢克斯平衡鹽溶液；腫瘤壞死因子 alpha

並列摘要

Microglia is an important cell type in the brain, which serves innate immunity functions as macrophages and dendritic cells. Aberrant function of microglia has been shown to contribute to inflammation responses and pathogenesis of various diseases in the brain. Previously many studies have explored the influences of hypoxia on the cellular functions of microglia; however, it is ill elucidated how nutrient deprivation affects the biology of microglia. In this study, we treated microglial cell line BV-2 with HBSS (Hank's Balanced Salt Solution) to mimic nutrient deprivation status and to explore the changed cell viability and signaling pathways that associated with inflammation. The major composition difference of HBSS compared to normal culture medium is deficiency of amino acids and vitamin, and glucose concentration is lower (1 g/L vs. 4.5 g/L). In our study, HBSS can induce microglial cell apoptosis, which is dependent on ROS production but not caspases activity. Increased ROS also contributes to signaling in multifaceted ways; ROS leads to activate AMPK but to inhibit ERK. HBSS-activated Syk can mediate ERK activity, and Syk activation was negatively regulated by ROS. HBSS can induce TNF- alpha production, and this effect was diminished by NAC, compound C and R406. Taken together, multiple signaling pathways are induced in microglial cells in response to HBSS, leading to TNF- alpha production and cell death.

並列關鍵字

Microglia ； Ischemic stroke ； Reactive oxygen species ； Tumor necrosis factor alpha

參考文獻

Akira S and Takeda K (2004) Toll-like receptor signaling. Nature Rev Immunol 4: 499-511.

Ashwell JD. (2006) The many paths to p38 mitogen-activated protein kinase activation in the immune system. Nat Rev Immunol 6:532–540.

Barone F.C, Irving E.A, Ray A.M, Lee J.C, Kassis S, Kumar S, Badger A.M, Legos J.J, Erhardt J.A, Ohlstein E.H, Hunter A.J, Harrison D.C, Philpott K, Smith B.R, Adams J.L, Parsons A.A. (2001) Inhibition of p38 mitogen-activated protein kinase provides neuroprotection in cerebral focal ischemia. Med Res Rev 21:129–145.

Carlson BW, Carlson JR, Neelon VJ, Hartman M (2008) Tailoring protocols to successfully recruit and retain older adults in a longitudinal study of sleep and cognition. Res Gerontol Nurs 4:232–237.

Caso JR, Pradillo JM, Hurtado O, Lorenzo P, Moro MA, Lizasoain I (2007) Toll-like receptor 4 is involved in brain damage and inflammation after experimental stroke. Circulation 115:1599–1608.

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探討營養缺乏於微膠細胞所誘導的訊息傳遞

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