Oleic acid ameliorates Aβ-induced inflammation by downregulation of COX-2 and iNOS via NFκB signaling pathway. (April 2015)

• Record Type: Journal Article
• Authors: Kim, Hyeri; Youn, Kumju; Yun, Eun-Young; Hwang, Jae-Sam; Jeong, Woo-Sik; Ho, Chi-Tang; Jun, Mira
• Is Part Of: Journal of functional foods. Volume 14(2015)
• Page Start: 1
• Page End: 11
• Publication Date: 2015-04
• Subjects: AD Alzheimer's disease -- Aβ amyloid β peptide -- APP amyloid peptide precursor -- β-secretase BACE1 -- ROS reactive oxygen species -- COX-2 cyclooxygenase -- iNOS inducible nitric oxide synthase -- NF-κB nuclear factor-κB -- MAPK mitogen-activated protein kinase -- ERK extracellular signal-regulated kinase -- JNK c-Jun-N-terminal kinase (JNK); Alzheimer's disease -- Amyloid β -- Oleic acid -- Inflammation -- NF-κB; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2015.01.027
• Languages: English
• ISSNs: 1756-4646

Abstract

Highlights: Aβ is a pivotal causal factor that initiates the neurotoxic cascade in AD. Oleic acid (OA) ameliorates Aβ-induced inflammation in PC12 cells. OA regulates the expression of iNOS and COX-2 with blockade of MAPK and NF-κB signaling pathway. Abstract: Beta-amyloid peptide (Aβ) damage is one of major potential causes of Alzheimer's disease (AD) and its modulation has emerged as a promising approach to control the onset of AD. In the present study, the effects of oleic acid (OA) against Aβ25–35 -stimulated neurotoxicity, inflammatory responses, and further molecular mechanism underlying the neuroprotective properties of OA in PC12 cells were investigated. Pre-treatment of OA significantly decreased Aβ25–35 -mediated cytotoxicity by increasing cell viability through the attenuation of intracellular reactive oxygen species (ROS) level and downregulation of pro-apoptotic activated caspase-3, thereby mitigating apoptotic morphological alterations. Improper up-regulation of both cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) by Aβ25–35 was significantly suppressed by preconditioning of OA through repression of the inhibitory unit I-κB degradation, which impedes subsequent nuclear translocation of the functionally active subunit of transcription factor nuclear factor-kappa B (NF-κB). OA noticeably attenuated Aβ25–35 -stimulated phosphorylation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK1/2), and c-Jun-N-terminal kinase (JNK). Taken together, these findings suggest that the mechanisms responsible for anti-apoptotic and anti-inflammatory properties of OA in Aβ25–35 -mediated neuronal damage is associated with COX-2 and iNOS downregulation through activation of NF-κB mediated by upstream kinases including JNK, ERK and p38 MAPK.