Resveratrol provides neuroprotective effects through modulation of mitochondrial dynamics and ERK1/2 regulated autophagy

Lin, Kai-Lieh; Wang, Pei‐Wen; Chuang, Jiin‐Haur; Lin, Hung‐Yu; Chen, Shang-Der; Chuang, Yao-Chung; Huang, Sheng‐Teng; Tiao, Mao‐Meng; Chen, Jin‐Bor; Huang, Pei-Hsuan; Liou, Chia‐Wei; Lin, Tsu-Kung

doi:10.1080/10715762.2018.1489128

Cited by 54 publications

(71 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The maintenance of mitochondrial membrane structure and physiological function depends on efficient mitochondrial function, which is restricted under hypoxic conditions 38 . It was reported that RSV modulates mitochondrial biogenesis and attenuates mitochondrial dysfunction, apoptosis and cell death in the rotenone-induced oxidative stress SH-SY5Y cellular Parkinson disease model 39,40 . In the present literature data, there is no report on the protective action of RSV against TRPM2 activation in cells during the HYPX.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol attenuates hypoxia-induced neuronal cell death, inflammation and mitochondrial oxidative stress by modulation of TRPM2 channel

Akyuva

Nazıroğlu

2020

Sci Rep

View full text Add to dashboard Cite

Hypoxia (HYpX) induced-overload ca 2+ entry results in increase of mitochondrial oxidative stress, inflammation and apoptosis in several neurons. Ca 2+ permeable TRPM2 channel was gated by ADPribose (ADPR) and reactive oxygen species (ROS), although its activity was modulated in HYPX-exposed neurons by resveratrol (RSV). The aim of this study was to evaluate if a therapy of RSV can modulate the effect of HYPX in the TRPM2 expressing SH-SY5Y neuronal and HEK293 (no expression of TRPM2) cell lines. The SH-SY5Y and HEK293 cells were divided into four groups as control, RSV (50 μM and 24 hours), and HYPX and RSV + HYPX. For induction of HYPX in the cells, CoCl 2 (200 μM and 24 hours) incubation was used. HYPX-induced intracellular Ca 2+ responses to TRPM2 activation were increased in the SH-SY5Y cells but not in the HEK293 cells from coming H 2 o 2 and ADPR. RSV treatment improved intracellular ca 2+ responses, mitochondrial function, suppressed the generation of cytokine (IL-1β and tnf-α), cytosolic and mitochondrial ROS in the SH-SY5Y cells. Intracellular free Zn 2+ , apoptosis, cell death, PARP-1, TRPM2 expression, caspase −3 and −9 levels are increased through activating TRPM2 in the SH-SY5Y cells exposed to the HYPX. However, the values were decreased in the cells by RSV and TRPM2 blockers (ACA and 2-APB). In SH-SY5Y neuronal cells exposed to HYPX conditions, the neuroprotective effects of RSV were shown to be exerted via modulation of oxidative stress, inflammation, apoptosis and death through modulation of TRPM2 channel. RSV could be used as an effective agent in the treatment of neurodegeneration exposure to HYPX.Extensive death in neurons was induced by acute hypoxia, because disability and mortality of the neurons were increased by acute hypoxia 1 . Low blood flow to the tissue and low oxygen content of blood result in hypoxia and ischemic condition 2 . Cell survival decreased in the absence of oxygen, because ATP generation requires oxygen consumption in mitochondria 3 . Mitochondria is a main source of reactive oxygen species (ROS) generation 4 . Accumulating evidence indicates that the hypoxia and ischemic conditions result in excessive ROS generation, inflammation and apoptosis through the increase of membrane depolarization in mitochondria of neurons 5,6 . The increase of mitochondrial membrane depolarization was induced by the increase of intracellular free Ca 2+ ([Ca 2+ ] i ) concentration. Recently, hypoxia-induced mitochondria ROS generation was inhibited through modulation of voltage gated calcium channel (VGCC) in the heart cells by resveratrol (RSV) treatment 7,8 . Hence, RSV can be useful for treatment of hypoxia in neuronal cells by modulation of mitochondrial ROS generation and the subject should be clarified in the hypoxia-induced SH-SY5Y neuronal cells.Several neuronal physiological functions such as mitochondria and cell development are triggered by the changes of the [Ca 2+ ] i concentration 4 . In addition, several neurotoxicity functions such as apoptosis and inflammation in hypoxia are...

show abstract

Section: Discussionmentioning

confidence: 99%

Resveratrol attenuates hypoxia-induced neuronal cell death, inflammation and mitochondrial oxidative stress by modulation of TRPM2 channel

Akyuva

Nazıroğlu

2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Furthermore, several studies have associated the neuroprotective effects of RV with its antioxidant properties. In this context, studies have shown that RV decreases ROS production and/or increases antioxidant defenses after the exposure to MPTP/MPP + (Okawara et al, 2007;Lu et al, 2008;Anandhan et al, 2010;da Rocha Lindner et al, 2015;Abolaji et al, 2018) and rotenone (Gaballah et al, 2016;Lin et al, 2018;Palle and Neerati, 2018). These results are supported by other studies showing that RV protects against mitochondrial dysfunction induced by experimental PD, counteracting the changes in mitochondrial morphology and mitochondrial membrane potential (∆Ψm; Zeng et al, 2017;Lin et al, 2018), as well as increasing mitochondrial biogenesis (Peng et al, 2016) and complex-I activity (Palle and Neerati, 2018).…”

Section: Neuroprotective Effects Of Resveratrol In Parkinson's Diseasementioning

confidence: 61%

“…Several substances are known to produce damage in dopaminergic neurons and have been used in experimental models of PD, including 6-OHDA (6-hydroxydopamine), MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and rotenone. In this context, in vitro studies have shown that RV is neuroprotective against the damage produced by 6-OHDA (Albani et al, 2009;Zhang et al, 2015), MPP + (a metabolite from MPTP; Gélinas and Martinoli, 2002;Alvira et al, 2007;Okawara et al, 2007;Bournival et al, 2009;Zeng et al, 2017) and rotenone (Lin et al, 2014(Lin et al, , 2018Feng et al, 2015;Wang et al, 2018a). These results are supported by studies in rodents showing that RV is neuroprotective against 6-OHDA (Jin et al, 2008;Huang et al, 2019), MPTP (Lu et al, 2008;Anandhan et al, 2010;da Rocha Lindner et al, 2015;Guo et al, 2016) and rotenone (Gaballah et al, 2016;Zhao et al, 2017;Palle and Neerati, 2018) counteracting the motor and cognitive changes induced by these neurotoxins as evidenced by several of these studies.…”

Section: Neuroprotective Effects Of Resveratrol In Parkinson's Diseasementioning

confidence: 83%

“…RV can exert protection against neuronal oxidative damage in different ways. It can increase the intracellular antioxidant levels, such as glutathione (Sharma and Gupta, 2002;Savaskan et al, 2003;Kwon et al, 2010) and antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and HO-1 (Chiang et al, 2018;Lin et al, 2018;Zhao et al, 2018;Kong et al, 2019), and decrease lipid peroxidation (Sharma and Gupta, 2002;Kong et al, 2019). Moreover, RV prevents the disruption of mitochondrial membrane potential, reducing ROS production in brain tissue (Kwon et al, 2010).…”

Section: Neuroprotective Effects Of Resveratrol In Alzheimer's Diseasementioning

confidence: 99%

See 1 more Smart Citation

Resveratrol Derivatives as Potential Treatments for Alzheimer’s and Parkinson’s Disease

Arbo

André‐Miral

Nasre-Nasser

et al. 2020

Front. Aging Neurosci.

View full text Add to dashboard Cite

Neurodegenerative diseases are characterized by the progressive loss of neurons in different regions of the nervous system. Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most prevalent neurodegenerative diseases, and the symptoms associated with these pathologies are closely related to the regions that are most affected by the process of neurodegeneration. Despite their high prevalence, currently, there is no cure or disease-modifying drugs for the treatment of these conditions. In the last decades, due to the need for the development of new treatments for neurodegenerative diseases, several authors have investigated the neuroprotective actions of naturally occurring molecules, such as resveratrol. Resveratrol is a stilbene found in several plants, including grapes, blueberries, raspberries, and peanuts. Studies have shown that resveratrol presents neuroprotective actions in experimental models of AD and PD, however, its clinical application is limited due to its rapid metabolism and low bioavailability. In this context, studies have proposed that structural changes in the resveratrol molecule, including glycosylation, alkylation, halogenation, hydroxylation, methylation, and prenylation could lead to the development of derivatives with enhanced bioavailability and pharmacological activity. Therefore, this review article aims to discuss how resveratrol derivatives could represent viable molecules in the search for new drugs for the treatment of AD and PD.

show abstract

“…Resveratrol induces apoptosis and autophagy by inhibiting Akt/mTOR and activating the p38-MAPK pathway [41]. It is reported that resveratrol exerts neuroprotective effects by modulating mitochondrial dynamics and upregulating autophagic flux via the MEK/ERK pathway [42]. OXY also changes the activity of p38 MAPK and PI3K/AKT/mTOR, which induces apoptosis cell death independent of autophagy [34].…”

Section: Discussionmentioning

confidence: 99%

Oxyresveratrol Induces Autophagy via the ER Stress Signaling Pathway, and Oxyresveratrol-Induced Autophagy Stimulates MUC2 Synthesis in Human Goblet Cells

Yeom

Lim

2020

Antioxidants

View full text Add to dashboard Cite

Background: Autophagy is a cell protection system invoked to eliminate the damaged organelles and misfolded proteins that induce various stresses, including endoplasmic reticulum (ER) stress. Autophagy can control mucin secretion in goblet cells. Oxyresveratrol (OXY), an antioxidant, stimulates expression of MUC2. Thus, we investigated the effect of OXY on autophagy and found that OXY-induced autophagy stimulates MUC2 expression in human intestinal goblet cells. Methods: Autophagy-related genes and proteins were examined by quantitative real-time PCR (qPCR) and Western blotting, respectively. Autophagy was assessed by immunocytochemistry (ICC). To analyze the protein expression profiles of OXY-treated LS 174T goblet cells, two-dimensional electrophoresis (2DE) and peptide mass fingerprinting (PMF) were performed. MUC2 expression in cells was evaluated by ICC. Results: OXY significantly increased the expression levels of genes related to autophagy induction, and activated phagosome elongation resulted in the formation of autophagosomes. OXY also activated the ER stress signaling pathway and promoted MUC2 synthesis, which was inhibited by treatment with an autophagy inhibitor. Conclusion: OXY induces autophagy via the ER stress signaling pathway, and OXY-induced autophagy increases MUC2 production in intestinal goblet cells.

show abstract

Resveratrol provides neuroprotective effects through modulation of mitochondrial dynamics and ERK1/2 regulated autophagy

Cited by 54 publications

References 77 publications

Resveratrol attenuates hypoxia-induced neuronal cell death, inflammation and mitochondrial oxidative stress by modulation of TRPM2 channel

Resveratrol attenuates hypoxia-induced neuronal cell death, inflammation and mitochondrial oxidative stress by modulation of TRPM2 channel

Resveratrol Derivatives as Potential Treatments for Alzheimer’s and Parkinson’s Disease

Oxyresveratrol Induces Autophagy via the ER Stress Signaling Pathway, and Oxyresveratrol-Induced Autophagy Stimulates MUC2 Synthesis in Human Goblet Cells

Contact Info

Product

Resources

About