醫(yī)學(xué)論文范文:外源磷脂酰乙醇胺誘導(dǎo)人宮頸癌HeLa細胞凋亡的研究

3 討論

磷脂酰乙醇胺是維持細胞膜不對稱性的重要磷脂成分。在正常細胞膜上，PE分布于細胞膜的內(nèi)側(cè)，而在細胞凋亡的過程中，其與PS一起外翻到細胞膜外側(cè)[10]。目前，大量研究認為PS外翻是細胞早期凋亡的信號，并參與細胞凋亡的發(fā)生。關(guān)于PE在細胞凋亡過程中的作用尚不清晰。本研究首次研究證明，外源PE可以顯著抑制Hela細胞的增殖，并發(fā)現(xiàn)PE對SMMC7721、HEK293以及HepG2具有相同的作用，表明PE細胞增殖抑制作用沒有細胞特異性(數(shù)據(jù)未顯)。

細胞增殖抑制受細胞增殖周期和細胞凋亡的雙重影響。細胞增殖檢測顯示PE在不同濃度下均不引起Hela細胞周期的改變，提示PE未通過細胞周期調(diào)控Hela細胞的生長抑制。凋亡檢測結(jié)果證明，PE明顯誘導(dǎo)了Hela細胞凋亡的發(fā)生。細胞凋亡指標與細胞生長抑制的結(jié)果一致。實驗表明，細胞凋亡是PE抑制細胞生長的主要方式醫(yī).學(xué)全.在.線jfsoft.net.cn。

PE是細胞膜不對稱分布的磷脂成分，在培養(yǎng)細胞時，提供外源PE，可能會引起細胞膜穩(wěn)定性下降，并誘導(dǎo)細胞凋亡。我們對HepG2進行研究時發(fā)現(xiàn)，PE處理細胞后，線粒體Δψm下降的細胞比例明顯增加，引起B(yǎng)cl��2表達下調(diào)以及Bax上調(diào)，以及caspase��3的激活。體外實驗證明，酸性磷脂和中性磷脂組成的脂質(zhì)體進行細胞色素c跨膜運送時，PE具有關(guān)鍵的作用。在PA∶PE∶PC體系中隨著PE 含量的增加, 細胞色素c跨膜運送增加[11]。關(guān)于PE是否通過線粒體通路誘導(dǎo)細胞凋亡，有待進一步的研究。

【參考文獻】

[1]HANSHAW RG, SMITH BD. New reagents for phosphatidylserine recognition and detection of apoptosis [J]. Bioorg Med Chem, 2005, 13(17):5035��5042.

[2]VAN MEER G, SIMONS K, OP DEN KAMP JA, et al. Phospholipid asymmetry in Semliki Forest virus grown on baby hamster kidney (BHK��21) cells [J]. Biochemistry, 1981, 20(7):1974��1981.

[3]DALEKE DL, LYLES JV. Identification and purification of aminophospholipid flippases [J]. Biochim Biophys Acta, 2000, 1486(1):108��127.

[4]KAMP D, SIEBERG T, HAEST CW. Inhibition and stimulation of phospholipid scrambling activity. Consequences for lipid asymmetry, echinocytosis, and microvesiculation of erythrocytes [J]. Biochemistry, 2001, 40(31):9438��9446.

[5]DAS P, ESTEPHAN R, BANERJEE P. Apoptosis is associated with an inhibition of aminophospholipid translocase (APTL) in CNS�瞕erived HN2��5 and HOG cells and phosphatidylserine is a recognition molecule in microglial uptake of the apoptotic HN2��5 cells [J]. Life Sci, 2003, 72(23):2617��2627.

[6]TYURINA YY, SHVEDOVA AA, KAWAI K, et al. Phospholipid signaling in apoptosis: peroxidation and externalization of phosphatidylserine [J]. Toxicology, 2000, 148(2��3):93��101.

[7]MATSURA T, TOGAWA A, KAI M, et al. The presence of oxidized phosphatidylserine Fas�瞞ediated apoptotic cell surface [J]. Biochim Biophys Acta, 2005, 1736(3):181��188.

[8]ISHII H, MORI T, SHIRATSUCHI A, et al. Distinct localization of lipid rafts and externalized phosphatidylserine at the surface of apoptotic cells [J]. Biochem Biophys Res Commun, 2005, 327(1):94��99.

[9]KELLER ET, FU Z, BRENNAN M. The role of Raf kinase inhibitor protein (RKIP) in health and disease [J]. Biochem Pharmacol, 2004, 68(6):1049��1053醫(yī).學(xué)全.在.線jfsoft.net.cn.

[10]WANG X, LI N, LIU B, et al. A novel human phosphatidylethanolamine�瞓inding protein resists tumor necrosis factor alpha�瞚nduced apoptosis by inhibiting mitogen�瞐ctivated protein kinase pathway activation and phosphatidylethanolamine externalization [J]. J Biol Chem, 2004, 279(44):45855��45864.

[11]MIAO Q, HAN X, YANG F. Phosphatidic acid�瞤hosphatidylethanolamine interaction and apocytochrome c translocation across model membranes [J]. Biochem J, 2001, 354(3):681��688.

上一頁  [1] [2] [3] [4]  下一頁