Inhibitory effects of procyanidin B(2) dimer on lipid-laden macrophage formation.
A proteomic analysis of procyanidin B(2) isolated from cocoa against oxidized low-density lipoprotein-induced lipid-laden macrophage formation was performed. Of approximately 400 detected proteins, 12 were differentially expressed as a result of B(2) treatment. They were subsequently identified by liquid chromatography-electrospray ionization-tandem mass spectrometry and the SWISS-PROT database. Further reverse transcriptase-polymerase chain reaction and Western blot analysis revealed that B(2) strongly inhibited arachidonic acid inflammatory reactions, apoptosis, and their coupled mitogen-activated protein kinase and NF-kappaB pathways. To highlight proteins or genes with similar expressed patterns and similarly biological function induced by B(2) in lipid-laden macrophages, a cluster and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed. The data were mapped to multiple pathways. Further validation of the bioinformatic results revealed that activation of Wnt signaling may contribute to the cardioprotection of B(2). The differentially expressed genes and proteins mentioned above induced by B(2) are through regulating nuclear transcription factors, activating peroxisome proliferator-activated receptor-gamma and inhibiting AP-1 mRNA expressions. These in vitro data help to interpret the beneficial effects of B(2) in reducing the risk of atherosclerosis after consumption of flavonoid-rich foods. Many differentially expressed genes induced by B(2) help to uncover novel targets and may help to target disease interactions in atherosclerosis in the future.
Chen
Dong-Mei
DM
Department of Pharmacology, Shanghai Institute of Materia Medica, Shanghai, China.
Cai
Xin
X
Kwik-Uribe
Catherine L
CL
Zeng
Rong
R
Zhu
Xing-Zu
XZ
D000595:Amino Acid Sequence; D001094:Arachidonate 5-Lipoxygenase / Q000032:analysis / Q000235:genetics; D044946:Biflavonoids / Q000494:pharmacology*; D002392:Catechin / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000032:analysis; D019281:Dimerization; D004734:Energy Metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008969:Molecular Sequence Data; D047495:PPAR gamma / Q000502:physiology; D044945:Proanthocyanidins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051127:Scavenger Receptors, Class E / Q000032:analysis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D020298:U937 Cells; D051153:Wnt Proteins / Q000502:physiology
D044946:Biflavonoids; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D047495:PPAR gamma; D044945:Proanthocyanidins; D012333:RNA, Messenger; D051127:Scavenger Receptors, Class E; D051153:Wnt Proteins; C099252:oxidized low density lipoprotein; C479580:procyanidin B2; D002392:Catechin; D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2