Resveratrol Inhibits β-Amyloid-Induced Neuronal Apoptosis through Regulation of SIRT1-ROCK1 Signaling Pathway

Abstract

Alzheimer’s disease (AD) is characterized by the accumulation of β-amyloid peptide (Aβ) and loss of neurons. Recently, a growing body of evidences have indicated that as a herbal compound naturally derived from grapes, resveratrol modulates the pathophysiology of AD, however, with a largely unclear mechanism. Therefore, we aimed to investigate the protection of resveratrol against the neurotoxicity of β-amyloid peptide 25–35 (Aβ25–35) and further explore its underlying mechanism in the present study. PC12 cells were injuried by Aβ25–35, and resveratrol at different concentrations was added into the culture medium. We observed that resveratrol increased cell viability through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) colorimetric assays. Flow cytometry indicated the reduction of cell apoptosis by resveratrol. Moreover, resveratrol also stabilized the intercellular Ca2+ homeostasis and attenuated Aβ25–35 neurotoxicity. Additionally, Aβ25–35-suppressed silent information regulator 1 (SIRT1) activity was significantly reversed by resveratrol, resulting in the downregulation of Rho-associated kinase 1 (ROCK1). Our results clearly revealed that resveratrol significantly protected PC12 cells and inhibited the β-amyloid-induced cell apoptosis through the upregulation of SIRT1. Moreover, as a downstream signal molecule, ROCK1 was negatively regulated by SIRT1. Taken together, our study demonstrated that SIRT1-ROCK1 pathway played a critical role in the pathomechanism of AD.

Resveratrol and its oligomers: modulation of sphingolipid metabolism and signaling in disease

“…No formal assessment has been made in relation to changes in sphingolipid levels in neurons after treatment with resveratrol. Nevertheless, neuroprotection has been consistently observed at <50 µM of resveratrol, which is lower than the concentration required to inhibit SK1 activity (K i = 160 ± 40 μM) and to induce apoptosis (Capiralla et al 2012;Chen et al 2005;Feng et al 2013;Lim et al 2012a;Marambaud et al 2005;Wang et al 2014). Therefore, low micromolar concentrations of resveratrol might mediate protection via a mechanism that does not involve changes in sphingolipid levels.…”

Targeting of microRNA‐199a‐5p protects against pilocarpine‐induced status epilepticus and seizure damage via SIRT1‐p53 cascade

“…For animals used for later EEG recordings, small stainless steel screw electrodes were also fixed in place. Rats were subjected to pilocarpine-induced status epilepticus (SE) 24 h later and euthanized at various time points after antagomir injection (1,3,7,14, and 60 days) for molecular analysis.…”

“…SIRT1 plays a pivotal role in a wide variety of cellular processes such as apoptosis/cell survival, endocrine signaling, chromatin remodeling, and gene transcription. 13 Recent studies have suggested that SIRT1 is an important endogenous apoptosis inhibitor in neurodegenerative disease, 14,15 and several studies have demonstrated that SIRT1 promotes mammalian axon regeneration and supports neurite outgrowth. 16 The miRNA miR199a has been found to target SIRT1 directly.…”

Natural Phenolic Compounds as Therapeutic and Preventive Agents for Cerebral Amyloidosis

“…Such effects have been reported in various phenolic compounds: flavones such as baicalein (Caruana et al 2012), flavonols such as Myr, quercetin, and morin (Ono et al 2003(Ono et al , 2006a(Ono et al , 2012Masuda et al 2006;Chakraborty et al 2011;Caruana et al 2012;Ho et al 2013), isoflavones such as glycitein and genistein , flavanols such as EGCG and theaflavins (Ono et al 2003(Ono et al , 2006aLevites et al 2003;Rezai-Zadeh et al 2005;Obregon et al 2006;Bastianetto et al 2006;Ehrnhoefer et al 2008;Bieschke et al 2010;He et al 2011;Grelle et al 2011;Cheng et al 2013;Sinha et al 2012;Rushworth et al 2013;Palhano et al 2013;Lorenzen et al 2014), stilbenes such as resveratrol, nordihydroguaiaretic acid (NDGA), piceid, and viniferin (Ono et al 2002(Ono et al , 2003(Ono et al , 2006a(Ono et al , 2012Savaskan et al 2003;Marambaud et al 2005;Rivière et al 2007Rivière et al , 2009Gauci et al 2011;Capiralla et al 2012;Ge et al 2012;Feng et al 2013;Vingtdeux et al 2010;Caruana et al 2012;Rushworth et al 2013;Richard et al 2013), phenolic acids such as rosmarinic acid (RA), tannic acids (TA), ferulic acid (FA), ellagic aci...…”