Pore formation by the cytotoxic islet amyloid peptide amylin

被引:372
作者
Mirzabekov, TA
Lin, MC
Kagan, BL
机构
[1] UNIV CALIF LOS ANGELES,INST NEUROPSYCHIAT,BRAIN RES INST,MENTAL RETARDAT RES CTR,LOS ANGELES,CA 90095
[2] UNIV CALIF LOS ANGELES,INST NEUROPSYCHIAT,BRAIN RES INST,MENTAL RETARDAT RES CTR,LOS ANGELES,CA 90095
[3] VET ADM MED CTR,LOS ANGELES,CA 90095
关键词
D O I
10.1074/jbc.271.4.1988
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Amylin is a 37-amino acid cytotoxic constituent of amyloid deposits found in the islets of Langerhans of patients with type II diabetes. Extracellular accumulation of this peptide results in damage to insulin-producting beta cell membranes and cell death. We report here that at cytotoxic concentrations, amylin forms voltage-dependent, relatively nonselective, ion-permeable channels in planar phospholipid bilayer membranes. Channel formation is dependent upon lipid membrane composition, ionic strength, and membrane potential, At 1-10 mu M, cytotoxic human amylin dramatically increases the conductance of lipid bilayer membranes, while noncytotoxic rat amylin does not. We suggest that channel formation may be the mechanism of cytotoxicity of human amylin.
引用
收藏
页码:1988 / 1992
页数:5
相关论文
共 34 条
  • [1] GIANT MULTILEVEL CATION CHANNELS FORMED BY ALZHEIMER-DISEASE AMYLOID BETA-PROTEIN [A-BETA-P-(1-40)] IN BILAYER-MEMBRANES
    ARISPE, N
    POLLARD, HB
    ROJAS, E
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (22) : 10573 - 10577
  • [2] CYCLIC CHANGES IN POTENTIAL AND RESISTANCE OF BETA-CELL MEMBRANE INDUCED BY GLUCOSE IN ISLETS OF LANGERHANS FROM MOUSE
    ATWATER, I
    RIBALET, B
    ROJAS, E
    [J]. JOURNAL OF PHYSIOLOGY-LONDON, 1978, 278 (MAY): : 117 - 139
  • [3] SEQUENCE DIVERGENCE IN A SPECIFIC REGION OF ISLET AMYLOID POLYPEPTIDE (IAPP) EXPLAINS DIFFERENCES IN ISLET AMYLOID FORMATION BETWEEN SPECIES
    BETSHOLTZ, C
    CHRISTMANSSON, L
    ENGSTROM, U
    RORSMAN, F
    SVENSSON, V
    JOHNSON, KH
    WESTERMARK, P
    [J]. FEBS LETTERS, 1989, 251 (1-2) : 261 - 264
  • [4] FORMATION OF ISLET AMYLOID FROM ISLET AMYLOID POLYPEPTIDE
    CLARK, A
    DEKONING, EJP
    MORRIS, JF
    [J]. BIOCHEMICAL SOCIETY TRANSACTIONS, 1993, 21 (01) : 169 - 173
  • [5] CLARK A, 1987, LANCET, V2, P231
  • [6] PURIFICATION AND CHARACTERIZATION OF A PEPTIDE FROM AMYLOID-RICH PANCREASES OF TYPE-2 DIABETIC-PATIENTS
    COOPER, GJS
    WILLIS, AC
    CLARK, A
    TURNER, RC
    SIM, RB
    REID, KBM
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (23) : 8628 - 8632
  • [7] CRYSTAL-STRUCTURES EXPLAIN FUNCTIONAL-PROPERTIES OF 2 ESCHERICHIA-COLI PORINS
    COWAN, SW
    SCHIRMER, T
    RUMMEL, G
    STEIERT, M
    GHOSH, R
    PAUPTIT, RA
    JANSONIUS, JN
    ROSENBUSCH, JP
    [J]. NATURE, 1992, 358 (6389) : 727 - 733
  • [8] MAGAININ-2, A NATURAL ANTIBIOTIC FROM FROG-SKIN, FORMS ION CHANNELS IN LIPID BILAYER-MEMBRANES
    CRUCIANI, RA
    BARKER, JL
    DURELL, SR
    RAGHUNATHAN, G
    GUY, HR
    ZASLOFF, M
    STANLEY, EF
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION, 1992, 226 (04): : 287 - 296
  • [9] INTRACELLULAR AND EXTRACELLULAR AMYLOID FIBRILS ARE FORMED IN CULTURED PANCREATIC-ISLETS OF TRANSGENIC MICE EXPRESSING HUMAN ISLET AMYLOID POLYPEPTIDE
    DEKONING, EJP
    MORRIS, ER
    HOFHUIS, FMA
    POSTHUMA, G
    HOPPENER, JWM
    MORRIS, JF
    CAPEL, PJA
    CLARK, A
    VERBEEK, JS
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (18) : 8467 - 8471
  • [10] ANION PORES FROM MAGAININS AND RELATED DEFENSIVE PEPTIDES
    DUCLOHIER, H
    [J]. TOXICOLOGY, 1994, 87 (1-3) : 175 - 188