Oxidative stress‐induced apoptosis and matrix loss of chondrocytes is inhibited by eicosapentaenoic acid

Sakata, S.; Hayashi, Shinya; Fujishiro, Takaaki; Kawakita, K.; Kanzaki, Noriyuki; Hashimoto, Shingo; Iwasa, Kenjiro; Chinzei, Nobuaki; Kihara, Shinsuke; Haneda, Masahiko; Ueha, Takeshi; Nishiyama, Tomihiro; Kuroda, Ryosuke; Kurosaka, Masahiro

doi:10.1002/jor.22767

Cited by 56 publications

(42 citation statements)

References 19 publications

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“…This DNA degradation was profoundly inhibited in the presence of NAC, a ROS scavenger, suggesting again the requirement of ROS in SNP-induced cell death [219]. Accordingly, intra-articular injection of antioxidants, such as N -acetylcysteine (NAC) or eicosapentaenoic acid (EPA), prevented cartilage destruction and apoptosis, in vivo, in a rat model of experimentally-induced OA [228] or in a DMM mouse model of OA [229], respectively. SNP-induced NO could induce cell death via the downstream production of ROS, NAC, neutralizing NO-induced ROS in rabbit cultured chondrocytes.…”

Section: Cell Death Regulators In Chondrocytesmentioning

confidence: 99%

“…The apoptosis-preventing activity of NAC was mediated by glutathione, as a glutathione synthetase inhibitor abrogated NAC protective effects [228]. In vitro, EPA and NAC were able to reduce SNP-induced caspase-3 cleavage, as well as p53 [228,229] and p38 phosphorylation [229]. Other studies have supported that NO was not able to induce apoptosis, as the production of high levels of endogenous NO (by adenoviral-mediated over-expression of the iNOS gene) in adenoviral transfected chondrocytes failed to induce cell death [230].…”

Section: Cell Death Regulators In Chondrocytesmentioning

confidence: 99%

“…Antioxidants have demonstrated anti-apoptotic and anti-OA effects in rat and mouse models [228,229]. Promoting autophagy could also indirectly act on removing defective mitochondria and the associated oxidative stress.…”

Section: Targeting Chondrocyte Apoptosis For Oa Treatmentmentioning

confidence: 99%

See 2 more Smart Citations

Insights on Molecular Mechanisms of Chondrocytes Death in Osteoarthritis

Charlier

Relić

Deroyer

et al. 2016

IJMS

266

220

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Osteoarthritis (OA) is a joint pathology characterized by progressive cartilage degradation. Medical care is mainly based on alleviating pain symptoms. Compelling studies report the presence of empty lacunae and hypocellularity in cartilage with aging and OA progression, suggesting that chondrocyte cell death occurs and participates to OA development. However, the relative contribution of apoptosis per se in OA pathogenesis appears complex to evaluate. Indeed, depending on technical approaches, OA stages, cartilage layers, animal models, as well as in vivo or in vitro experiments, the percentage of apoptosis and cell death types can vary. Apoptosis, chondroptosis, necrosis, and autophagic cell death are described in this review. The question of cell death causality in OA progression is also addressed, as well as the molecular pathways leading to cell death in response to the following inducers: Fas, Interleukin-1β (IL-1β), Tumor Necrosis factor-α (TNF-α), leptin, nitric oxide (NO) donors, and mechanical stresses. Furthermore, the protective role of autophagy in chondrocytes is highlighted, as well as its decline during OA progression, enhancing chondrocyte cell death; the transition being mainly controlled by HIF-1α/HIF-2α imbalance. Finally, we have considered whether interfering in chondrocyte apoptosis or promoting autophagy could constitute therapeutic strategies to impede OA progression.

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Section: Cell Death Regulators In Chondrocytesmentioning

confidence: 99%

Section: Cell Death Regulators In Chondrocytesmentioning

confidence: 99%

See 1 more Smart Citation

Insights on Molecular Mechanisms of Chondrocytes Death in Osteoarthritis

Charlier

Relić

Deroyer

et al. 2016

IJMS

266

220

View full text Add to dashboard Cite

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“…The activation of MAPKs regulates downstream redox-sensitive transcription factors, such as p53 and Nrf2, to control the expression of downstream pro-apoptotic and anti-apoptotic genes [30, 31]. Nrf2 regulates the transcription of a number of antioxidant enzymes by binding to the antioxidant response element (ARE) in the promoter regions of genes such as glutathione synthesis enzymes and thioredoxin-1, among others, and regulates the expression of the anti-apoptotic gene Bcl-2 .…”

Section: Discussionmentioning

confidence: 99%

Elevated Apoptosis in the Liver of Dairy Cows with Ketosis

Chen

Huang

et al. 2017

Cell Physiol Biochem

106

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Background/Aims: Dairy cows with ketosis are characterized by oxidative stress and hepatic damage. The aim of this study was to investigate hepatic oxidative stress and the apoptotic status of ketotic cows, as well as the underlying apoptosis pathway. Methods: The blood aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH) and gamma-glutamyl transferase (GGT) activities and the haptoglobin (HP), serum amyloid A (SAA) and serum apoptotic cytokeratin 18 neo-epitope M30 (CK18 M30) concentrations were determined by commercially available kits and ELISA kits, respectively. Liver histology, TUNEL and Oil red O staining were performed in liver tissue samples. TG contents were measured using an enzymatic kit; Caspase 3 assays were carried out using the Caspase 3 activity assay kit; oxidation and antioxidant markers were measured using biochemical kits; apoptosis pathway were determined by qRT-PCR and western blot. Results: Ketotic cows displayed hepatic fat accumulation. The hepatic malondialdehyde (MDA) content was significantly increased, but the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were markedly decreased in ketotic cows compared with control cows, indicating that ketotic cows displayed severe oxidative stress. Significantly higher serum levels of the hepatic damage markers AST, ALT, GGT and GLDH were observed in ketotic cows than in control cows. The blood concentration of the apoptotic marker CK18 M30 and the number of TUNEL-positive cells in the liver of ketotic cows were 1.19- and 2.61-fold, respectively, higher than the values observed in control cows. Besides, Caspase 3 activity was significantly increased in the liver of ketosis cows. Importantly, the levels of phosphorylated c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) were significantly increased but the level of phosphorylated extracellular signal-regulated kinase1/2 (ERK1/2) was markedly decreased, which further promoted tumor protein 53 (p53) expression and inhibited nuclear factor E2-related factor 2 (Nrf2) expression. The apoptosis-related molecules p21, MDM2, Caspase 3, Caspase 9 and Bax were expressed at significantly higher levels in ketotic cows than in healthy cows, whereas the anti-apoptosis molecule Bcl-2 was expressed at significantly lower levels. Conclusions: Based on these results, ketotic cows display severe hepatic oxidative stress. The hepatic MAPK-p53-Nrf2 apoptotic pathway is over induced and partially mediated apoptotic damage in the liver.

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“…The level of chondrocyte degeneration is correlated with the pathogenesis of osteoarthritis (OA), the most common chronic joint disease [35][36][37]. At the molecular level, Shuhei Sakata et al evaluated the effects of EPA on OA and found that EPA dramatically inhibited sodium nitroprusside (SNP)-induced chondrocyte apoptosis by suppressing phosphorylation of p38 mitogen-activated protein kinase (MAPK) and p53, caspase 3 and poly(ADP-ribose) polymerase cleavage, and expression of matrix metalloproteinases (MMPS) (Figure 3) [38].…”

Section: Cardioprotective Effectmentioning

confidence: 99%

Researches on the Pharmacological Effects of Eicosapentaenoic Acid

Pang¹,

Zhang²,

Tian³

et al. 2015

Journal of Pharmaceutics and Drug Development

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Fish oils are the most common source of omega-3 polyunsaturated fatty acids (n-3 PUFAs), mainly eicosapentaenoic acid (EPA). It has been pointed out protective effects and beneficial effects of EPA on body weight reduction, heart health, blood lipid profile, cardiovascular diseases and other diseases. Based on its biological activities, EPA may be developed to a complementary and alternative medicine through further research. In this paper, the pharmacological effects of EPA were summarized by reviewing the recent related literatures.Abstract ISSN: 2348-9782 In the late 1970s, Dyerberg et al. [1] highlighted the cardio protective effect of dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) for the first time. As the decades passed, n-3 PUFAs have been developed as dietary supplements, and it is now widely accepted that n-3PUFAs are incorporated as structural components into cell membrane phospholipids in the blood and tissues, and they mediate an array of biological effects [2,3]. Keywords: Eicosapentaenoic acid; Pharmacological effects; Research progressEicosapentaenoic acid (EPA) is typical omega-3 polyunsaturated fatty acids found in fish and fish oils, and it is derived from another n-3 PUFA, α-linolenic acid (α-LNA) ( Figure 1) [4][5][6]. Many reports have shown that EPA has protective roles against many diseases. This paper reviewed the main pharmacological effects of EPA, which provided reference to further study and develop EPA. The pharmacological effects of EPA Obesity is considered as an important public health disease, along with at least three of the following: abdominal obesity, hypertension, hyperglycemia, reduced plasma high-density lipoprotein (HDL), cholesterol and elevated plasma triglyceride (TG). Given the side effects and limitations of pharmacologic therapies, it is greatly needed to develop nutritional interventions which may not only prevent or treat obesity but also inhibit its associated diseases. Some studies reported that n-3 PUFAs had positive effects on body weight reduction [7,8]. Furthermore, the effect of EPA supplementation on overweight has been scarcely investigated and its therapeutic effects have been confirmed.In a review of randomized controlled trials, Monique J LeMieux et al. [9] investigated the possible mechanisms to explain the antilipogenic effect of EPA. The results showed that supplementation with EPA in the high fat diet could prevent diet-induced obesity and insulin resistance. Both glucose homeostasis and metabolic profile were ameliorated by reducing adipose tissue inflammation, and this was done possibly through the reduction of lipid accumulation, prostaglandin (PG) synthesis and adipocyte size ( Figure 2). A clinical trial showed that the supplementation with EPA combination with α-lipoic acid at lower doses (300mg/day) could promote fat mass reduction and weight loss in healthy overweight women following an energy-restricted balanced diet [10]. Anti-lipogenic effectAlthough increasing evidence have showed that consumption of EPA could decrease ris...

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Oxidative stress‐induced apoptosis and matrix loss of chondrocytes is inhibited by eicosapentaenoic acid

Cited by 56 publications

References 19 publications

Insights on Molecular Mechanisms of Chondrocytes Death in Osteoarthritis

Insights on Molecular Mechanisms of Chondrocytes Death in Osteoarthritis

Elevated Apoptosis in the Liver of Dairy Cows with Ketosis

Researches on the Pharmacological Effects of Eicosapentaenoic Acid

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