Modulation of 4HNE-Mediated Signaling by Proline-Rich Peptides from Ovine Colostrum
| Autor: | Jerzy A. Georgiades, T. Kley Hughes, G. John Stanton, Terry L. Juelich, Marian L. Kruzel, Daniel Liebenthal, Istvan Boldogh |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Biology
Lipid peroxidation Cellular and Molecular Neuroscience chemistry.chemical_compound Western blot Alzheimer Disease medicine Animals Neurons chemistry.chemical_classification Aldehydes Reactive oxygen species Sheep medicine.diagnostic_test Kinase Colostrum JNK Mitogen-Activated Protein Kinases General Medicine Glutathione Rats Colostrinin Oxidative Stress chemistry Biochemistry Intercellular Signaling Peptides and Proteins Lipid Peroxidation Mitogen-Activated Protein Kinases Tumor Suppressor Protein p53 Signal transduction Peptides Reactive Oxygen Species Intracellular Signal Transduction |
| Zdroj: | Journal of Molecular Neuroscience. 20:125-134 |
| ISSN: | 0895-8696 |
| DOI: | 10.1385/jmn:20:2:125 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink