Role of 4-hydroxynonenal in stress-mediated apoptosis signaling

Mol Aspects Med. Aug-Oct 2003;24(4-5):219-30. doi: 10.1016/s0098-2997(03)00017-7.


In this mini review we summarize recent studies from our laboratory, which show the involvement of 4-hydroxynonenal (4-HNE) in cell cycle signaling. We demonstrate 4-HNE induced apoptosis in various cell lines is accompanied with c-Jun-N-terminal kinase and caspase-3 activation. Cells exposed to mild, transient, heat or oxidative stress acquire capacity to exclude intracellular 4-HNE at a faster rate by inducing hGST5.8 which conjugate 4-HNE to GSH, and RLIP76 which mediates the ATP-dependent transport of the GSH-conjugate of 4-HNE. The cells preconditioned with mild transient stress acquire resistance to H(2)O(2) and 4-HNE induced apoptosis by excluding intracellular 4-HNE at an accelerated pace. Furthermore, a decrease in intracellular concentration of 4-HNE achieved by transfecting cells with mGSTA4-4 or hGSTA4-4 results in a faster growth rate. These studies strongly suggest a role of 4-HNE in stress mediated signaling.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • ATP-Binding Cassette Transporters*
  • Aldehydes / metabolism*
  • Animals
  • Apoptosis / immunology
  • Apoptosis / physiology*
  • Carrier Proteins / immunology
  • Caspase 3
  • Caspases / metabolism
  • GTPase-Activating Proteins*
  • Glutathione Transferase / metabolism
  • Hydrogen Peroxide / metabolism
  • Lipid Peroxidation / physiology
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • Signal Transduction / physiology*
  • Transcription Factor AP-1 / metabolism


  • ATP-Binding Cassette Transporters
  • Aldehydes
  • Carrier Proteins
  • GTPase-Activating Proteins
  • RALBP1 protein, human
  • Transcription Factor AP-1
  • Hydrogen Peroxide
  • Glutathione Transferase
  • Mitogen-Activated Protein Kinases
  • CASP3 protein, human
  • Casp3 protein, mouse
  • Caspase 3
  • Caspases
  • 4-hydroxy-2-nonenal