Islet Amyloid Polypeptide Membrane Interactions: Effects of Membrane Composition.
Islet Amyloid Polypeptide Membrane Interactions: Effects of Membrane Composition.
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DOI：
10.1021/acs.biochem.6b01016
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发表时间：
2017-01-17
期刊：
影响因子：
2.9
通讯作者：
Raleigh DP
中科院分区：
文献类型：
--
作者：
Zhang X;St Clair JR;London E;Raleigh DP
胰岛淀粉样多肽（IAPP）形成淀粉样蛋白导致2型糖尿病β细胞功能障碍。β细胞膜的扰动可能导致IAPP诱导的毒性。我们研究了脂质成分、盐和缓冲液对IAPP淀粉样蛋白形成和IAPP诱导模型膜渗漏的能力的影响。即使是低水平的阴离子脂质也会促进淀粉样蛋白的形成和膜透化。增加阴离子脂质、POPS或DOPG的百分比，提高淀粉样蛋白形成的速率并增加膜透化。两性离子脂质的选择对膜催化的淀粉样蛋白形成没有显著影响，但在大多数情况下影响渗漏，渗漏倾向于以DOPC>POPC>鞘磷脂的顺序降低。增加膜有序性的不带电荷的脂质降低了IAPP诱导渗漏的能力。在这些研究条件下，渗漏主要是由于孔形成而不是囊泡的完全破坏。胆固醇处于或低于生理水平显著降低囊泡催化的IAPP淀粉样蛋白形成的速率，并降低对IAPP诱导的渗漏的易感性。胆固醇对淀粉样蛋白形成的影响被25摩尔%的POPS掩盖。总的来说，形成淀粉样蛋白的时间和囊泡渗漏的程度之间存在很强的负相关性。NaCl降低了阴离子囊泡膜催化淀粉样蛋白形成的速率，但加速了溶液中淀粉样蛋白的形成。IAPP膜相互作用的影响进行了讨论，是磷脂酰丝氨酸不对称性的损失，增强IAPP淀粉样蛋白的形成和膜损伤在体内通过正反馈回路的可能性。
Amyloid formation by islet amyloid polypeptide (IAPP) contributes to β-cell dysfunction in type-2 diabetes. Perturbation of the β-cell membrane may contribute to IAPP induced toxicity. We examine the effects of lipid composition, salt and buffer on IAPP amyloid formation and on the ability of IAPP to induce leakage of model membranes. Even low levels of anionic lipids promote amyloid formation and membrane permeabilization. Increasing the percentage of the anionic lipids, POPS or DOPG, enhances the rate of amyloid formation and increases membrane permeabilization. The choice of zwitterionic lipid has no noticeable effect on membrane catalyzed amyloid formation, but in most cases affects leakage, which tends to decrease in the order DOPC>POPC>sphingomyelin. Uncharged lipids that increase membrane order reduce the ability of IAPP to induce leakage. Leakage is due predominately to pore formation rather than complete disruption of the vesicles under the conditions of these studies. Cholesterol at or below physiological levels significantly reduces the rate of vesicle catalyzed IAPP amyloid formation and decreases susceptibility to IAPP induced leakage. The effects of cholesterol on amyloid formation are masked by 25 mole percent POPS. Overall, there is a strong inverse correlation between the time to form amyloid and the extent of vesicle leakage. NaCl reduces the rate of membrane catalyzed amyloid formation by anionic vesicles, but accelerates amyloid formation in solution. The implications for IAPP membrane interactions are discussed, as is the possibility that loss of phosphatidylserine asymmetry enhances IAPP amyloid formation and membrane damage in vivo via a positive feedback loop.
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影响因子：
4.3
作者：
Akter R;Cao P;Noor H;Ridgway Z;Tu LH;Wang H;Wong AG;Zhang X;Abedini A;Schmidt AM;Raleigh DP
通讯作者：
Raleigh DP
影响因子：
2.9
作者：
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通讯作者：
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影响因子：
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作者：
Despa S;Sharma S;Harris TR;Dong H;Li N;Chiamvimonvat N;Taegtmeyer H;Margulies KB;Hammock BD;Despa F
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影响因子：
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