Journal of Molecular Neuroscience

, Volume 20, Issue 2, pp 125–134 | Cite as

Modulation of 4HNE-mediated signaling by proline-rich peptides from ovine colostrum

  • Istvan Boldogh
  • Daniel Liebenthal
  • T. Kley Hughes
  • Terry L. Juelich
  • Jerzy A. Georgiades
  • Marian L. Kruzel
  • G. John StantonEmail author
Original Article


In previous studies we showed that colostrinin (CLN), a complex of proline-rich polypeptides derived from ovine colostrum, induces mitogenic stimulation, as well as a variety of cytokines in human peripheral blood leukocytes, and possesses antioxidant activity in pheochromocytoma (PC12) cells. In this study we investigated the effects of CLN on 4-hydroxynonenal (4HNE)-mediated adduct formation, generation of reactive oxygen species (ROS), glutathione (GSH) metabolism, and the modification of signal transduction cascade that leads to activation of c-Jun N-terminal kinase (JNK) in PC12 cells. Here we demonstrate that CLN (1) reduced the abundance of 4HNE-protein adducts, as shown by fluorescent microscopy and Western blot analysis; (2) reduced intracellular levels of ROS, as shown by a decrease in 2′,7′-dichlorodihydro-fluorescein-mediated fluorescence; (3) inhibited 4HNE-mediated GSH depletion, as determined fluorimetrically; and (4) inhibited 4HNE-induced activation of JNKs. Together, these findings suggest that CLN appears to down-regulate 4HNE-mediated lipid peroxidation and its product-induced signaling that otherwise may lead to pathological changes at the cellular and organ level. These findings also suggest further that CLN could be useful in the treatment of diseases such as Alzheimer’s, as well as those in which ROS are implicated in pathogenesis.

Index Entries

Colostrum colostrinin 4HNE ROS 


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Copyright information

© Humana Press Inc 2003

Authors and Affiliations

  • Istvan Boldogh
    • 1
  • Daniel Liebenthal
    • 1
  • T. Kley Hughes
    • 1
  • Terry L. Juelich
    • 1
  • Jerzy A. Georgiades
    • 2
  • Marian L. Kruzel
    • 2
  • G. John Stanton
    • 1
    Email author
  1. 1.Department of Microbiology and ImmunologyThe University of Texas Medical BranchGalveston
  2. 2.ReGen Therapeutics, PlcLondonEngland

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