Large procyanidins prevent bile-acid-induced oxidant production and membrane-initiated ERK1/2, p38, and Akt activation in Caco-2 cells

Autor: Grayson K. Jaggers, Alejandra G. Erlejman, Patricia I. Oteiza, Mathieu Da Silva, Cesar G. Fraga, Sandra V. Verstraeten
Rok vydání: 2012
Předmět:
Cell
Free radicals
Apoptosis
p38 Mitogen-Activated Protein Kinases
Biochemistry
Antioxidants
Polymerization
Cell membrane
chemistry.chemical_compound
Bile
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
NADPH oxidase
biology
Deoxycholic acid
Membrane
Bioquímica y Biología Molecular
Oxidants
medicine.anatomical_structure
Signal transduction
Colorectal Neoplasms
CIENCIAS NATURALES Y EXACTAS
Deoxycholic Acid
Signal Transduction
Cell Survival
Ciencias Biológicas
Physiology (medical)
medicine
Humans
Proanthocyanidins
Protein kinase B
Procyanidins
Flavonoids
Dose-Response Relationship
Drug
Cell Membrane
NADPH Oxidases
MAPK
Colorectal cancer
Bile acids
Enzyme Activation
chemistry
Caco-2
biology.protein
Calcium
Caco-2 Cells
Proto-Oncogene Proteins c-akt
Intestinal epithelial cells
Zdroj: Free Radical Biology and Medicine. 52:151-159
ISSN: 0891-5849
DOI: 10.1016/j.freeradbiomed.2011.10.436
Popis: Procyanidins are oligomers of flavanol subunits present in large amounts in fruits and vegetables. Their consumption is associated with health benefits against colonic inflammation and colorectal cancer (CRC). Large procyanidins (with more than three subunits) are not absorbed by intestinal epithelial cells but could exert biological actions through their interactions with the cell membrane. This study investigated the capacity of hexameric procyanidins (Hex) to prevent oncogenic events initiated by deoxycholic acid (DCA), a secondary bile acid linked to the promotion of CRC. Hex interacted with Caco-2 cell membranes preferentially at the water–lipid interface. Hex (2.5–20 μM) inhibited DCA-triggered increase in cellular calcium, NADPH oxidase activation, and oxidant production. DCA promoted the activation of protein kinase B (Akt), of the mitogen-activated protein kinases ERK1/2 and p38, and of the downstream transcription factor AP-1. This activation was not triggered by calcium or oxidant increases. Hex caused a dose-dependent inhibition of DCA-mediated activation of all these signals. DCA also triggered alterations in the cell monolayer morphology and apoptotic cell death, events that were delayed by Hex. The capacity of large procyanidins to interact with the cell membrane and prevent those cell membrane-associated events can in part explain the beneficial effects of procyanidins on CRC. Fil: Da Silva, Mathieu. University of California at Davis; Estados Unidos Fil: Jaggers, Grayson K.. University of California at Davis; Estados Unidos Fil: Verstraeten, Sandra Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Erlejman, Alejandra Giselle. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Fraga, Cesar Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Bioquímica y Medicina Molecular; Argentina. University of California at Davis; Estados Unidos Fil: Oteiza, Patricia Isabel. University of California at Davis; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Databáze: OpenAIRE
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