Attenuation of age-related changes in FOXO3a activity and the PI3K/Akt pathway by short-term feeding of ferulate

Abstract

Ferulate (4-hydroxy-3-methoxycinnamic acid) is a well-known phenolic compound that scavenges free radicals and exerts anti-inflammatory effects. Forkhead box O3a (FOXO3a), a transcription factor that plays important roles in aging processes, decreases with age and is negatively regulated through phosphorylation by phosphatidylinositol 3-kinase (PI3K)/Akt signaling. The present study investigated the efficacy of short-term ferulate feeding on age-related changes in PI3K/Akt/FOXO3a and upstream insulin signaling pathways in aged rats. In addition, changes in manganese superoxide dismutase (MnSOD) and catalase expression were examined because of their dependence on PI3K/Akt/FOXO3a activity. Short-term feeding experiments were done with a diet containing ferulate that was given to aged rats at doses of 3 or 6 mg kg −1 day −1 for 10 days.Results showed that FOXO3a activity was increased in the ferulate-fed old group compared with the control old group. Also, ferulate suppressed the PI3K/Akt signaling pathway that is responsible for FOXO3a inhibition in aged rats. Plasma insulin levels and the upstream insulin signaling pathway were also modulated by ferulate correspondingly with PI3K/ Akt/FOXO3a activity. The age-related decrease in two major antioxidant enzymes, MnSOD and catalase, was blunted by ferulate, which was accompanied by FOXO3a transcriptional activity. The significance of the present study is the finding that short-term feeding of ferulate effectively modulates age-related renal FOXO3a, PI3K/Akt and insulin signaling pathways, and MnSOD and catalase expression, all of which may be beneficial for attenuating the aging process.

Suppression of melanogenesis by a newly synthesized compound, MHY966 via the nitric oxide/protein kinase G signaling pathway in murine skin

“…Western blotting was performed as described previously [12]. Homogenized samples were boiled for 5 min in gel-loading buffer (125 mM Tris-HCl, 4% SDS, 10% 2-mercaptoethanol, pH 6.8, and 0.2% bromophenol blue) at a 1:1 ratio.…”

FoxO3a suppresses the senescence of cardiac microvascular endothelial cells by regulating the ROS-mediated cell cycle

“…The phosphorylation of FoxO3a by Akt leads to its association with 14-3-3 proteins and subsequent nuclear exclusion, retention, and degradation in the cytoplasm, which deactivates the FoxO3a pathway [1,2]. Conversely, the inhibition of Akt phosphorylation, which results in the dephosphorylation, nuclear translocation, and activation of FoxO3a, leads to the expression of target genes associated with aging [3], apoptosis [4], oxidative stress [5], and cell cycle progression [6]. Thus, this protein exhibits different functions based on cell type.…”

“…In particular, oxidative stress is considered a major factor contributing to the aging process and leads to aberrant signaling pathways. Aged rats have increased oxidative stress and weakened antioxidative defense systems [3]. Therefore, it is necessary to attenuate oxidative stress and strengthen the antioxidant system to modulate altered signaling pathway molecules to constrain the aging process.…”

Correlation between Three Pregnancy Characteristics (Age, Parity, βhCG Level) and pAkt Immunoexpression on Complete Hydatidiform Mole

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“…The expression of Akt itself increases with age. Choi et al [19] showed that ferulate administration in rats can suppress Akt activity, and thus inhibit the aging process.…”