Apoptosis

, Volume 14, Issue 7, pp 878–889

Sphingomyelinase dependent apoptosis following treatment of pancreatic beta-cells with amyloid peptides Aß1-42 or IAPP

  • Ying Zhang
  • Felicia Ranta
  • Cai Tang
  • Ekaterina Shumilina
  • Hasan Mahmud
  • Michael Föller
  • Susanne Ullrich
  • Hans-Ulrich Häring
  • Florian Lang
Original Paper

DOI: 10.1007/s10495-009-0364-4

Cite this article as:
Zhang, Y., Ranta, F., Tang, C. et al. Apoptosis (2009) 14: 878. doi:10.1007/s10495-009-0364-4

Abstract

Amyloid peptides interfere with survival of pancreatic beta-cells. In some cells apoptosis is paralleled by ceramide-dependent alterations of ion channel activity. The purpose of the present study was to elucidate the dependence of amyloid peptides Aß1-42 and islet amyloid polypeptide (IAPP)-induced cell death on ceramide formation and ion channel activity in murine pancreatic islet cells. As disclosed by TUNEL (terminal dUTP nick-end labelling) and cleaved caspase 3 staining, apoptotic cell death was induced by Aß1-42, IAPP and exogenously added C2-ceramide in islet cells from wild type mice. In islet cells from acid sphingomyelinase-deficient mice (ASMKO) Aß1-42 and IAPP but not exogenously added N-acetyl-d-sphingosine (C2-ceramide, 20 μM) failed to stimulate apoptosis. Immunofluorescent staining revealed a stimulatory effect of Aß1-42 on ceramide formation. According to patch clamp experiments, administration of Aß1-42 and IAPP significantly decreased outwardly rectifying whole cell currents in wild type but not in ASMKO islet cells. C2-ceramide but not inactive di-ceramide (20 μM) mimicked the inhibitory effect on Kv channel current. In conclusion, amyloid peptides induce apoptosis of pancreatic islet cells at least in part through activation of acid sphingomyelinase resulting in production of ceramide and subsequent inhibition of ion channel activity.

Keywords

CeramideKv channelsCell deathInsulinAmylin

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Ying Zhang
    • 1
  • Felicia Ranta
    • 2
  • Cai Tang
    • 1
  • Ekaterina Shumilina
    • 1
  • Hasan Mahmud
    • 1
  • Michael Föller
    • 1
  • Susanne Ullrich
    • 2
  • Hans-Ulrich Häring
    • 2
  • Florian Lang
    • 1
    • 3
  1. 1.Department of PhysiologyUniversity of TübingenTübingenGermany
  2. 2.Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical ChemistryUniversity of TübingenTübingenGermany
  3. 3.Physiologisches Institut der Universität TübingenTübingenGermany