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 Stanton

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)125-134
Number of pages10
JournalJournal of Molecular Neuroscience
Volume20
Issue number2
DOIs
StatePublished - Apr 2003

Fingerprint

Colostrum
Proline
Sheep
Modulation
Peptides
Reactive Oxygen Species
PC12 Cells
Chemical activation
Signal transduction
JNK Mitogen-Activated Protein Kinases
Pheochromocytoma
Fluorescein
Metabolism
Lipid Peroxidation
Glutathione
Microscopy
Signal Transduction
Microscopic examination
Leukocytes
Blood

Keywords

  • 4HNE
  • Colostrinin
  • Colostrum
  • ROS

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry
  • Genetics

Cite this

Boldogh, I., Liebenthal, D., Hughes, T. K., Juelich, T. L., Georgiades, J. A., Kruzel, M. L., & Stanton, G. J. (2003). Modulation of 4HNE-mediated signaling by proline-rich peptides from ovine colostrum. Journal of Molecular Neuroscience, 20(2), 125-134. https://doi.org/10.1385/JMN:20:2:125

Modulation of 4HNE-mediated signaling by proline-rich peptides from ovine colostrum. / Boldogh, Istvan; Liebenthal, Daniel; Hughes, T. Kley; Juelich, Terry L.; Georgiades, Jerzy A.; Kruzel, Marian L.; Stanton, G. John.

In: Journal of Molecular Neuroscience, Vol. 20, No. 2, 04.2003, p. 125-134.

Research output: Contribution to journalArticle

Boldogh, I, Liebenthal, D, Hughes, TK, Juelich, TL, Georgiades, JA, Kruzel, ML & Stanton, GJ 2003, 'Modulation of 4HNE-mediated signaling by proline-rich peptides from ovine colostrum', Journal of Molecular Neuroscience, vol. 20, no. 2, pp. 125-134. https://doi.org/10.1385/JMN:20:2:125
Boldogh, Istvan ; Liebenthal, Daniel ; Hughes, T. Kley ; Juelich, Terry L. ; Georgiades, Jerzy A. ; Kruzel, Marian L. ; Stanton, G. John. / Modulation of 4HNE-mediated signaling by proline-rich peptides from ovine colostrum. In: Journal of Molecular Neuroscience. 2003 ; Vol. 20, No. 2. pp. 125-134.
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