Formation of insulin fragments by insulin-degrading enzyme: the role of zinc(II) and cystine bridges

被引：35

作者：

Bellia, Francesco ^{[1
]}

Pietropaolo, Adriana ^{[2
]}

Grasso, Giuseppe ^{[3
]}

机构：

[1] CNR, Ist Biostrutture & Bioimmagini, Catania, Italy

[2] Univ Catanzaro, Dipartimento Sci Salute, I-88100 Catanzaro, Italy

[3] Univ Catania, Dipartimento Sci Chim, I-95125 Catania, Italy

来源：

JOURNAL OF MASS SPECTROMETRY | 2013年 / 48卷 / 02期

关键词：

insulin; IDE; reduction; mass spectrometry; diabetes; B-CHAIN; DEGRADATION; METABOLISM; TARGETS; PROTEIN; MICE;

D O I：

10.1002/jms.3060

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Insulin is the hormone mainly involved in widespread diseases such as diabetes mellitus. It is widely recognized that metal ions such as zinc(II) as well as insulin degradation and insulin fragments are inexplicably linked to the hormone action. Insulin-degrading enzyme (IDE) has been identified as the main factor of insulin degradation, but it is still unknown the exact way and location at which IDE action toward insulin occurs and how metal ions can modulate this interaction. Interestingly, some insulin fragments have different biological activity from the intact hormone, and it is not clear how they can be generated from insulin. In this work, the role of zinc(II) and cystine bridges in the degradation of insulin by IDE are investigated by high-performance liquid chromatography-mass spectrometry (HPLC-MS), and the experimental conditions at which peculiar insulin fragments having biological activity are formed by the action of IDE are found and discussed. Docking simulations of IDE/insulin A and B chains are in good accordance with the insulin fragments detected by HPLC-MS. Copyright (c) 2013 John Wiley & Sons, Ltd.

引用

页码：135 / 140

页数：6

共 32 条

[1] Human Insulin-Degrading Enzyme Working Mechanism [J].

Amata, Orazio ;

Marino, Tiziana ;

Russo, Nino ;

Toscano, Marirosa .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2009, 131 (41) :14804-14811

[2] Endosomal proteolysis of internalized insulin at the C-terminal region of the B chain by cathepsin D [J].

Authier, F ;

Métioui, M ;

Fabrega, S ;

Kouach, M ;

Briand, G .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (11) :9437-9446

[3] AN UNUSUAL ACTIVE-SITE IDENTIFIED IN A FAMILY OF ZINC METALLOENDOPEPTIDASES [J].

BECKER, AB ;

ROTH, RA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (09) :3835-3839

[4]

Brange J, 1993, Pharm Biotechnol, V5, P315

[5] Protection of nonobese diabetic mice from diabetes by intranasal or subcutaneous administration of insulin peptide B-(9-23) [J].

Daniel, D ;

Wegmann, DR .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (02) :956-960

[6] The HADDOCK web server for data-driven biomolecular docking [J].

De Vries, Sjoerd J. ;

van Dijk, Marc ;

Bonvin, Alexandre M. J. J. .

NATURE PROTOCOLS, 2010, 5 (05) :883-897

[7] Biological activity of a fragment of insulin [J].

Duckworth, WC ;

Fawcett, J ;

Tsui, BT ;

Bennett, RG ;

Hamel, FG .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2004, 318 (04) :1019-1024

[8] Insulin degradation: Progress and potential [J].

Duckworth, WC ;

Bennett, RG ;

Hamel, FG .

ENDOCRINE REVIEWS, 1998, 19 (05) :608-624

[9]

DUCKWORTH WC, 1994, J LAB CLIN MED, V124, P311

[10] Insulin-degrading enzyme regulates the levels of insulin, amyloid β-protein, and the β-amyloid precursor protein intracellular domain in vivo [J].

Farris, W ;

Mansourian, S ;

Chang, Y ;

Lindsley, L ;

Eckman, EA ;

Frosch, MP ;

Eckman, CB ;

Tanzi, RE ;

Selkoe, DJ ;

Guénette, S .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (07) :4162-4167

← 1 2 3 4 →