Ferulic Acid Attenuates the Injury-Induced Decrease of Protein Phosphatase 2A Subunit B in Ischemic Brain Injury

Abstract

BackgroundFerulic acid provides a neuroprotective effect during cerebral ischemia through its anti-oxidant function. Protein phosphatase 2A (PP2A) is a serine and threonine phosphatase that contributes broadly to normal brain function. This study investigated whether ferulic acid regulates PP2A subunit B in a middle cerebral artery occlusion (MCAO) animal model and glutamate toxicity-induced neuronal cell death.Methodology/Principal FindingsMCAO was surgically induced to yield permanent cerebral ischemic injury in rats. The rats were treated with either vehicle or ferulic acid (100 mg/kg, i.v.) immediately after MCAO, and cerebral cortex tissues were collected 24 h after MCAO. A proteomics approach, RT-PCR, and Western blot analyses performed to identification of PP2A subunit B expression levels. Ferulic acid significantly reduced the MCAO-induced infarct volume of the cerebral cortex. A proteomics approach elucidated the reduction of PP2A subunit B in MCAO-induced animals, and ferulic acid treatment prevented the injury-induced reduction in PP2A subunit B levels. RT-PCR and Western blot analyses also showed that ferulic acid treatment attenuates the injury-induced decrease in PP2A subunit B levels. Moreover, the number of PP2A subunit B-positive cells was reduced in MCAO-induced animals, and ferulic acid prevented these decreases. In cultured neuronal cells, ferulic acid treatment protected cells against glutamate toxicity and prevented the glutamate-induced decrease in PP2A subunit B.Conclusions/SignificanceThese results suggest that the maintenance of PP2A subunit B by ferulic acid in ischemic brain injury plays an important role for the neuroprotective function of ferulic acid.

Focal cerebral ischemic injury decreases calbindin expression in brain tissue and HT22 cells

“…Western blot analysis was performed as previously described with some modification [16,17]. The ischemic regions of right cerebral cortices ( n =5 per group) were lysed in lysis buffer [1% Triton X-100, 1 mM EDTA in 1×PBS (pH 7.4)] containing 10 µM leupeptin and 200 µM phenylmethylsulfonyl fluoride.…”

“…Immunohistochemistry was performed as in a previously described method [17]. Brain tissues ( n =5 per group) were fixed in 4% paraformaldehyde in 0.1 M phosphate-buffered saline (PBS, pH 7.4) and embedded in paraffin.…”

Sodium selenate, a protein phosphatase 2A activator, mitigates hyperphosphorylated tau and improves repeated mild traumatic brain injury outcomes

“…PP2A heterotrimers consisting of the PR55 regulatory B-subunit (PP2A/PR55) account for over 70% of tau phosphatase activity in the brain and is essential for the dephosphorylation of tau Liu et al, 2005;Shi, 2009;Wang et al, 1996Wang et al, , 2007Xu et al, 2008). Importantly, the downregulation of PP2A/PR55 occurs after brain insult (Chen et al, 2010;Koh, 2013;Shultz et al, 2015c), and promotes h-tau (Bolognin et al, 2012;Sontag et al, 2004). As such, PP2A/PR55 may be affected by mTBI and contribute to h-tau, and up-regulating PP2A/PR55 may reduce h-tau and improve outcomes in the rmTBI setting.…”

Ferulic acid ameliorates chronic constriction injury induced painful neuropathy in rats

“…FA has also been reported as anti-inflammatory (Gohil et al 2012;Murakami et al 2002), anti-diabetic (Mancuso and Santangelo 2014;Ohnishi et al 2004;Song et al 2014), hepatoprotective (Krishnan et al 2013;Kim et al 2011;Al Maruf et al 2015;Panneerselvam et al 2013), anti-hyperlipidemic, andanti-atherogenic (Marimuthu et al 2013;Kwon et al 2010), neuroprotective Koh 2012Koh , 2013, anti-cancer, and anti-apoptotic effects (Serafim et al 2011;Thakkar et al 2014). However, the potential usefulness of this compound has not yet been explored in painful neuropathy.…”