Hydroxytyrosol prevents chondrocyte death under oxidative stress by inducing autophagy through sirtuin 1-dependent and -independent mechanisms

Cetrullo, Silvia; D’Adamo, Stefania; Guidotti, Silvia; Borzı̀, Rosa Maria; Flamigni, Flavio

doi:10.1016/j.bbagen.2016.03.002

Cited by 68 publications

(81 citation statements)

References 42 publications

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“…Wu Cellular Physiology and Biochemistry Cellular Physiology and Biochemistry et al [56] found that OA chondrocytes had lower autophagic level and higher level of ROS production compared with the normal chondrocytes. Cetrullo et al [57] demonstrated that oxidative stress inhibited the expression of autophagy-related proteins in chondrocytes and promoted apoptosis. Even though a close (negative) relationship between autophagy and apoptosis has been previously suggested, the role of autophagy in the chondroprotective effect of adiponectin has not been explored.…”

Section: Ampk/mtor Signaling Pathway Is Involved In Gapn-induced Automentioning

confidence: 99%

Globular Adiponectin Attenuated H2O2-Induced Apoptosis in Rat Chondrocytes by Inducing Autophagy Through the AMPK/ mTOR Pathway

Cui

Ding

et al. 2017

Cell Physiol Biochem

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Background/Aims: Chondrocyte apoptosis is closely related to the development and progression of osteoarthritis. Global adiponectin (gAPN), secreted from adipose tissue, possesses potent anti-inflammatory and antiapoptotic properties in various cell types. This study aimed to investigate the role of autophagy induced by gAPN in the suppression of H 2 O 2 -induced apoptosis and the potential mechanism of gAPN-induced autophagy in chondrocytes. Methods: H 2 O 2 was used to induce apoptotic injury in rat chondrocytes. CCK-8 assay was performed to determine the viability of cells treated with different concentrations of gAPN with or without H 2 O 2 . Cell apoptosis was detected by flow cytometry and TUNEL staining. Mitochondrial membrane potential was examined using JC-1 fluorescence staining assay. The autophagy inhibitors 3-MA and Bafilomycin A1 were used to treat cells and then evaluate the effect of gAPN-induced autophagy. To determine the downstream pathway, chondrocytes were preincubated with the AMPK inhibitor Compound C. Beclin-1, LC3B, P62 and apoptosisrelated proteins were identified by Western blot analysis. Results: H 2 O 2 (400 μM)-induced chondrocytes apoptosis and caspase-3 activation were attenuated by gAPN (0.5 μg/mL). gAPN increased Bcl-2 expression and decreased Bax expression. The loss of mitochondrial membrane potential induced by H 2 O 2 was also abolished by gAPN. Furthermore, the antiapoptotic effect of gAPN was related to gAPN-induced autophagy by increased formation of Beclin-1 and LC3B and P62 degradation. In particular, the inhibition of gAPN-induced autophagy by 3-MA prevented the protective effect of gAPN on apoptosis induced by H 2 O 2 . Moreover, gAPN increased p-AMPK expression and decreased p-mTOR expression. Compound C partly suppressed the expression of autophagy-related proteins and restored the expression of p-mTOR suppressed by gAPN. Thus, the AMPK/mTOR pathway played an important role

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Section: Ampk/mtor Signaling Pathway Is Involved In Gapn-induced Automentioning

confidence: 99%

Globular Adiponectin Attenuated H2O2-Induced Apoptosis in Rat Chondrocytes by Inducing Autophagy Through the AMPK/ mTOR Pathway

Cui

Ding

et al. 2017

Cell Physiol Biochem

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“…Its pathogenesis is complex, and oxidative stress is a critical factor contributing to the progression of this disease. Autophagy is a degradation process that can respond to the rise of cellular oxidative stress, and can be linked to the development of DN [23][24][25] . Past studies have found that increased UII expression is associated with not only oxidative stress level induced by DN, but also the progression of DN 26,27 .…”

Section: Discussionmentioning

confidence: 99%

Retraction statement: ‘Urotensin II inhibits autophagy in renal tubular epithelial cells and induces extracellular matrix production in early diabetic mice’ by Guan‐Jong Chen, Fei Wu, Xin‐Xin Pang, Ai‐Hua Zhang, Jun‐Bao Shi, Min Lu and Chao‐Shu Tang

Chen

Pang

et al. 2016

J of Diabetes Invest

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Aims/Introduction: Urotensin II (UII) and autophagy have been considered as important components in the pathogenesis of diabetic nephropathy. The present study explores whether UII can regulate autophagy in the kidney, and its effect in diabetes. Materials and Methods: Immunohistochemistry and western blot were carried out on the kidney tissues of diabetic UII receptor (UT) gene knockout mice, wild-type diabetic mice and normal control mice. For the in vitro experiment, HK-2 cells were treated with UII (10 -7 mol/L) in the presence or absence of UT antagonist, SB-657510, (10 -6 mol/L) or autophagy inducer, rapamycin (10 -3 mol/L), for 12 h. Markers for autophagy (LC3-II, p62/ SQSTM1) and extracellular matrix (fibronectin, collagen IV) were analyzed. Results: In diabetic UT knockout mice, expression of LC3-II is increased and p62 was reduced in comparison with that of the normal diabetic mice. Fibronectin and collagen IV were downregulated in diabetic UT knockout mice when compared with that of the normal diabetic mice. For the in vitro cell experiment, UII was shown to inhibit expression LC3-II and increase expression of p62 in comparison with that of the normal control. Treatment with SB-657510 can block UII-induced downregulation of LC3-II and upregulation of p62 while inhibiting UII-induced upregulation of fibronectin and collagen IV. Adding autophagy inducer, rapamycin, also inhibited UII-induced upregulation of fibronectin and collagen IV.Conclusions: The present study is the first to show that UII can downregulate autophagy in the kidney while accompanying the increased production of extracellular matrix in early diabetes. Our in vitro study also showed that upregulation of autophagy can decrease UII-induced production of extracellular matrix in HK-2 cells.

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Section: Protective Properties Of Hydroxytyrosolmentioning

confidence: 99%

“…Recently, Cetrullo et al [14] studied the possibility of modulating autophagy in chondrocytes through the treatment with HT, by assessment of DNA damage and cell death in human C-28/12 chondrocytes undergoing primary osteoarthritis when exposed to hydrogen peroxide. HT increased autophagy markers and protected chondrocytes from DNA damage and cell death induced by OS [14]. Furthermore, in rats submitted to severe exercise for an 8-week period, supplementation with 25 mg/kg/day of HT reduced OS and thereby mitochondrial impairment, with reduction of muscular atrophy induced by autophagy and mitochondrial fission [58] (Table 1).…”

Section: Protective Properties Of Hydroxytyrosolmentioning

confidence: 99%

“…In this context, hydroxytyrosol (HT) (3,4-Dihydroxyphenyl)ethanol; Figure 1) is a polyphenol mainly present in extra virgin olive oil (EVOO) [4] that has a potent antioxidant activity [5,6,7]. Moreover, HT provides other beneficial benefits that may be of importance for human health [8], namely anti-inflammatory [9] and anticancer [10] effects, enhancement of endothelial and vascular function [11], anti-steatotic [7,12] properties, and improvement of endoplasmic reticulum stress [13], autophagy [14] and mitochondrial function [15]. Interestingly, HT is the only polyphenol recognized by the European Food Safety Authority as a protector of low density lipoproteins (LDL) from oxidative damage [16], considering the finding that HT reduces the expression of adhesion molecules in endothelial cells, preventing the oxidation of LDL [17].…”

Section: Introductionmentioning

confidence: 99%

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Hydroxytyrosol and Cytoprotection: A Projection for Clinical Interventions

Echeverría

Ortíz

Valenzuela

et al. 2017

IJMS

105

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Hydroxytyrosol (HT) ((3,4-Dihydroxyphenyl)ethanol) is a polyphenol mainly present in extra virgin olive oil (EVOO) but also in red wine. It has a potent antioxidant effect related to hydrogen donation, and the ability to improve radical stability. The phenolic content of olive oil varies between 100 and 600 mg/kg, due to multiple factors (place of cultivation, climate, variety of the olive and level of ripening at the time of harvest), with HT and its derivatives providing half of that content. When consumed, EVOO’s phenolic compounds are hydrolyzed in the stomach and intestine, increasing levels of free HT which is then absorbed in the small intestine, forming phase II metabolites. It has been demonstrated that HT consumption is safe even at high doses, and that is not genotoxic or mutagenic in vitro. The beneficial effects of HT have been studied in humans, as well as cellular and animal models, mostly in relation to consumption of EVOO. Many properties, besides its antioxidant capacity, have been attributed to this polyphenol. The aim of this review was to assess the main properties of HT for human health with emphasis on those related to the possible prevention and/or treatment of non-communicable diseases.

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Hydroxytyrosol prevents chondrocyte death under oxidative stress by inducing autophagy through sirtuin 1-dependent and -independent mechanisms

Cited by 68 publications

References 42 publications

Globular Adiponectin Attenuated H2O2-Induced Apoptosis in Rat Chondrocytes by Inducing Autophagy Through the AMPK/ mTOR Pathway

Globular Adiponectin Attenuated H2O2-Induced Apoptosis in Rat Chondrocytes by Inducing Autophagy Through the AMPK/ mTOR Pathway

Retraction statement: ‘Urotensin II inhibits autophagy in renal tubular epithelial cells and induces extracellular matrix production in early diabetic mice’ by Guan‐Jong Chen, Fei Wu, Xin‐Xin Pang, Ai‐Hua Zhang, Jun‐Bao Shi, Min Lu and Chao‐Shu Tang

Hydroxytyrosol and Cytoprotection: A Projection for Clinical Interventions

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