Inhibition of glycosaminoglycan-mediated amyloid formation by islet amyloid polypeptide and proIAPP processing intermediates.
Inhibition of glycosaminoglycan-mediated amyloid formation by islet amyloid polypeptide and proIAPP processing intermediates.
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DOI：
10.1016/j.jmb.2010.12.028
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发表时间：
2011-02-25
影响因子：
5.6
通讯作者：
Raleigh DP
中科院分区：
文献类型：
--
作者：
Meng F;Raleigh DP
胰岛淀粉样蛋白多肽（IAPP，淀粉不溶素）负责2型糖尿病中的胰岛淀粉样蛋白形成，并且认为IAPP诱导的毒性有助于与2型糖尿病晚期相关的β细胞质量损失。胰岛淀粉样蛋白的形成也可能在移植后的移植失败中起作用。IAPP作为激素原proIAPP产生，并在胰腺β细胞的分泌颗粒中加工。在淀粉样蛋白沉积物中发现了部分加工形式的proIAPP;最值得注意的是，48个残基的中间体proIAPP 1 -48，其包括N-末端pro延伸，但在C-末端已被适当加工。不完全加工可能通过促进与细胞外基质的硫酸化蛋白聚糖的相互作用而在胰岛淀粉样蛋白形成中起作用，这反过来又促进淀粉样蛋白形成。我们发现，酸性品红（3-（1-（4-氨基-3-甲基-5-磺酸基苯基）-1-（4-氨基-3-磺酸基苯基）亚甲基）环己-1，4-二烯磺酸），一种简单的磺化三苯基甲基衍生物，是一种有效的抑制淀粉样蛋白形成的proIAPP 1 -48中间体。更复杂的三苯甲烷衍生物快速绿色FCF，{乙基-[4-[[4-[乙基-[（3-磺基苯基）甲基]氨基]苯基]-（4-羟基-2-磺基苯基）亚甲基]-1-环己-2，5-二烯亚基]-[（3-磺基苯基）甲基]吖丙啶}，也通过IAPP和proIAPP加工中间体抑制淀粉样蛋白形成。两种化合物均通过proIAPP中间体和模型糖胺聚糖（GAG）硫酸乙酰肝素的混合物抑制淀粉样蛋白形成。酸性品红还抑制成熟IAPP引起的GAG介导的淀粉样蛋白形成。抑制淀粉样蛋白形成的能力不仅仅是由于化合物被磺化，因为Aβ淀粉样蛋白反式酸的磺化抑制剂不是proIAPP 1 -48形成淀粉样蛋白的抑制剂。
Islet amyloid polypeptide, (IAPP, Amylin), is responsible for islet amyloid formation in type 2 diabetes and IAPP induced toxicity is believed to contribute to the loss of β-cell mass associated with the late stages of type 2 diabetes. Islet amyloid formation may also play a role in graft failure after transplantation. IAPP is produced as a prohormone, proIAPP, and processed in the secretory granules of the pancreatic beta cells. Partially processed forms of proIAPP are found in amyloid deposits; most notably, a 48 residue intermediate, proIAPP1–48, which includes the N-terminal pro extension, but which has been properly processed at the C-terminus. Incomplete processing may plays a role in islet amyloid formation by promoting interactions with sulfated proteoglycans of the extracellular matrix which, in turn, promote amyloid formation. We show that acid fuchsin (3-(1-(4-Amino-3-methyl-5-sulphonatophenyl)-1-(4-amino-3-sulphonatophenyl) methylene) cyclohexa-1,4-dienesulphonic acid), a simple sulfonated triphenyl methyl derivative, is a potent inhibitor of amyloid formation by the proIAPP1–48 intermediate. The more complicated triphenyl methane derivative fast green FCF, {ethyl-[4-[[4-[ethyl -[(3-sulfophenyl) methyl] amino] phenyl]-(4-hydroxy-2- sulfophenyl) methylidene]-1-cyclohexa-2,5-dienylidene]-[(3-sulfophenyl) methyl] azanium}, also inhibits amyloid formation by IAPP and the proIAPP processing intermediate. Both compounds inhibit amyloid formation by mixtures of the proIAPP intermediate and the model glycosaminoglycan (GAG) heparan sulfate. Acid fuchsin also inhibits GAG mediated amyloid formation by mature IAPP. The ability to inhibit amyloid formation is not simply due to the compounds being sulfonated, since the sulfonated inhibitor of Aβ amyloid tramprosate, is not an inhibitor of amyloid formation by proIAPP1–48.
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影响因子：
2.9
作者：
Abedini, A;Singh, G;Raleigh, DP
通讯作者：
Raleigh, DP
影响因子：
--
作者：
Andersson A;Bohman S;Borg LA;Paulsson JF;Schultz SW;Westermark GT;Westermark P
通讯作者：
Westermark P
DOI：
10.1073/pnas.84.23.8628
发表时间：
1987-12-01
影响因子：
11.1
作者：
COOPER, GJS;WILLIS, AC;REID, KBM
通讯作者：
REID, KBM
影响因子：
8.2
作者：
HUTTON, JC
通讯作者：
HUTTON, JC
影响因子：
14.8
作者：
Feng, Brian Y.;Toyama, Brandon H.;Shoichet, Brian K.
通讯作者：
Shoichet, Brian K.