Hsp22 Inhibits Oxidative Stress-Induced Endplate Chondrocyte Apoptosis by Regulating Mitochondrial Pathway

2021 ◽  
Vol 11 (10) ◽  
pp. 1947-1954
Author(s):  
Yi Ye ◽  
Xucan Wang ◽  
Zhenqing Yang ◽  
Qian Xu ◽  
Bo Zhang
Keyword(s):  
Oxidative Stress ◽  
Cell Apoptosis ◽  
Facet Joint ◽  
Mitochondrial Pathway ◽  
Chondrocyte Apoptosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Ros Generation ◽  
Atp Level ◽  
Facet Joint Degeneration ◽  
Cyt C

Background: Facet joint degeneration (FJD), which is also called facet joint syndrome (FJS), has become one of the most commonly seen etiological factors for lumbago. Cartilage lesion triggered by lumbar facet joint (LFJ) degeneration might be related to mitochondrial impairment, but the its underlying mechanism remains unclear. Materials and methods: The endplate chondrocytes were induced by hydrogen peroxide (H2O2) to mimic the pathological conditions of oxidative stress. Enzyme linked immunosorbent assay (ELISA) were used for the evaluation of reactive oxygen species (ROS). Adenosine-triphosphate (ATP) level was assessed using ATP detection, along with the detection the expression of cytochrome C in mitochondria (mito-cyt c) and in cell cytoplasm (cyto-cyt c) and cleaved caspase 3 by Western blot analysis. TUNEL assay was conducted for the measurement of cell apoptosis in endplate chondrocytes. Reverse transcription-polymerase chain reaction (RT-qPCR) was used to verify the expression of heat shock protein 22 (HSP22) and the transfection efficiency of HSP22 interference plasmid. Results: It was found that H2O2 promoted the mitochondrial dysfunction, ROS generation and cell apoptosis in endplate chondrocytes. Moreover, HSP22 was down-regulated in H2O2-induced endplate chondrocytes, and interference of HSP22 decreased the ROS production, increased the ATP level and promoted the cell apoptosis, resulting in the enhanced impairment of endplate chondrocytes. Additionally, mitochondrial ROS inhibitor (Mito-TEMPO) ameliorated the injury effects of HSP22 silencing in the H2O2-induced endplate chondrocytes. Conclusion: In conclusion, HSP22 inhibits oxidative stress-induced endplate chondrocyte apoptosis by regulating mitochondrial pathway, possibly providing novel guidance direction for the treatment of LFJ degeneration.

scholarly journals Honokiol ameliorates oxidative stress-induced DNA damage and apoptosis of c2c12 myoblasts by ROS generation and mitochondrial pathway

2019 ◽  
Vol 24 (1) ◽  
pp. 60-68 ◽  
Author(s):  
Cheol Park ◽  
Sung Hyun Choi ◽  
Jin-Woo Jeong ◽  
Min Ho Han ◽  
Hyesook Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Mitochondrial Pathway ◽  
Ros Generation ◽  
C2c12 Myoblasts

scholarly journals The REDD1/TXNIP Complex Accelerates Oxidative Stress-Induced Apoptosis of Nucleus Pulposus Cells through the Mitochondrial Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-22
Author(s):  
Huipeng Yin ◽  
Kun Wang ◽  
Abhirup Das ◽  
Gaocai Li ◽  
Yu Song ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Cell Apoptosis ◽  
Redox Homeostasis ◽  
Mitochondrial Pathway ◽  
Nucleus Pulposus Cells ◽  
Damage Response ◽  
Induced Apoptosis ◽  
Ivd Degeneration

The death of nucleus pulposus (NP) cells is an important cause of intervertebral disc (IVD) degeneration. Redox disturbance caused by dysfunctional mitochondria has been considered as a vital risk for NP cell survival. It is valuable to identify key proteins maintaining mitochondrial function in NP cells. A previous study found that regulated in development and DNA damage response 1 (REDD1) are upregulated during intervertebral disc degeneration and that REDD1 can cause NP cell apoptosis. Thus, the present study further explores the effect of REDD1 on IVD degeneration. Our results showed that REDD1 promotes NP cell apoptosis via the mitochondrial pathway. Importantly, REDD1 formed a complex with TXNIP to strengthen its own action, and the combination was consolidated under H2O2-induced oxidative stress. The combined inhibition of the REDD1/TXNIP complex was better than that of REDD1 or TXNIP alone in restoring cell proliferation and accelerating apoptosis. Moreover, p53 acts as the transcription factor of REDD1 to regulate the REDD1/TXNIP complex under oxidative stress. Altogether, our results demonstrated that the REDD1/TXNIP complex mediated H2O2-induced human NP cell apoptosis and IVD degeneration through the mitochondrial pathway. Interferences on these sites to achieve mitochondrial redox homeostasis may be a novel therapeutic strategy for oxidative stress-associated IVD degeneration.

scholarly journals Cul4a as a New Interaction Protein of PARP1 Inhibits Oxidative Stress-Induced H9c2 Cell Apoptosis

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Ning Ye ◽  
Naijin Zhang ◽  
Ying Zhang ◽  
Hao Qian ◽  
Boquan Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Apoptosis ◽  
Protective Factor ◽  
Core Protein ◽  
Ros Generation ◽  
H9c2 Cell ◽  
Protective Function ◽  
Protection Mechanism ◽  
Ubiquitin Ligase Complex ◽  
Ros Formation

Oxidative stress plays a major part in myocardial reperfusion injury. Cul4a is the core protein of CRLs E3 ubiquitin ligase complex; while it is known that Cul4a is responsible for various cancers, its role in cardiac function remains unclear. Hence, we have shown the protective function of Cul4a and its protection mechanism in oxidative stress-induced H9c2 cardiomyocyte apoptosis. Here, oxidative stress was induced by hydrogen peroxide (H2O2), CCK-8 assay and flow cytometry were used to analyze cell viability and apoptosis rate, western blot and immunofluorescence were used to quantitatively analyze the expression of protein, ROS fluorescence kit was used to detect reactive oxygen species (ROS) formation, and coimmunoprecipitation was used to identify protein interaction. In the results, it was found that Cul4a was involved in oxidative stress-induced H9c2 cell apoptosis and could inhibit H2O2-induced ROS generation and H9c2 cell apoptosis. Furthermore, we identified that when combining with PARP1, Cul4a could reduce its expression, and the interaction was enhanced under oxidative stress. In conclusion, our results indicate that Cul4a is a new protective factor involved in oxidative stress-induced cardiomyocyte injury and functions by tying and decreasing overactivated PARP1.

scholarly journals Polydatin Prevents Methylglyoxal-Induced Apoptosis through Reducing Oxidative Stress and Improving Mitochondrial Function in Human Umbilical Vein Endothelial Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Ningbo Pang ◽  
Tangting Chen ◽  
Xin Deng ◽  
Ni Chen ◽  
Rong Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Mitochondrial Function ◽  
Cell Apoptosis ◽  
Umbilical Vein ◽  
Ros Generation ◽  
Mitochondrial Morphology ◽  
Human Umbilical Vein ◽  
Induced Apoptosis ◽  
Umbilical Vein Endothelial Cells

Methylglyoxal (MGO), an active metabolite of glucose, has been reported to induce vascular cell apoptosis in diabetic complication. Polydatin (PD), a small natural compound from Polygonum cuspidatum, has a number of biological functions, such as antioxidative, anti-inflammatory, and nephroprotective properties. However, the protective effects of PD on MGO-induced apoptosis in endothelial cells remain to be elucidated. In this study, human umbilical vein endothelial cells (HUVECs) were used to explore the effects of PD on MGO-induced cell apoptosis and the possible mechanism involved. HUVECs were pretreated with PD for 2 h, followed by stimulation with MGO. Then cell apoptosis, reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP) impairment, mitochondrial morphology alterations, and Akt phosphorylation were assessed. The results demonstrated that PD significantly prevented MGO-induced HUVEC apoptosis. PD pretreatment also significantly inhibited MGO-induced ROS production, MMP impairment, mitochondrial morphology changes, and Akt dephosphorylation. These results and the experiments involving N-acetyl cysteine (antioxidant), Cyclosporin A (mitochondrial protector), and LY294002 (Akt inhibitor) suggest that PD prevents MGO-induced HUVEC apoptosis, at least in part, through inhibiting oxidative stress, maintaining mitochondrial function, and activating Akt pathway. All of these data indicate the potential application of PD for the treatment of diabetic vascular complication.

Reduction of oxidative stress and apoptosis in hyperlipidemic rats by composite oil (CO) of Sesamum indicum L. and Vicia faba L.

2021 ◽  
pp. 1-11
Author(s):  
Holima Khatun ◽  
Mousumi Mitra ◽  
Koushik Das ◽  
Atiskumar Chattopadhyay ◽  
Dilip Kumar Nandi
Keyword(s):  
Oxidative Stress ◽  
Vicia Faba ◽  
Rat Model ◽  
Cell Apoptosis ◽  
Seed Oil ◽  
Treated Group ◽  
Ros Generation ◽  
Group Iii ◽  
Tnf Α ◽  
Group Ii

BACKGROUND: Hyperlipidemia associated with cardiovascular diseases (CVDs) is a global health issue that can be alleviated by functional foods. OBJECTIVES: The present study aimed to investigate the effect of composite oil (CO) of sesame seed oil (SSiO) and Vicia faba seed oil (SVfO) on inflammatory factors, ROS generation level, and cell apoptosis level on high lipid diet (HLD) induced hyperlipidemic rat model. METHODS: Hyperlipidemic rat model was developed by feeding HLD to the experimental rats for eight weeks. Male albino rats weighing around 200–210 g were randomly divided into three equal groups: group I: control, received a normal diet; group II: received HLD for eight weeks, group III: received the HLD with CO orally. After 60 days of treatment, the levels of C-reactive protein (CRP), interleukin (IL)-10; tumor necrosis factor (TNF)-α, IL-18, reactive oxygen species (ROS), and cell apoptosis were serially assessed. RESULTS: After eight weeks of CO treatment, TNF- α, IL-18, CRP, and oxidative ROS generation significantly decreased in CO treated group (group III) compared to group II. On the other hand, IL-10 levels significantly increased in CO treated group compared to group II animals. It was also observed that the percentage of the late apoptotic cell reduced considerably in the CO treated group (group III) compared to HLD-fed animals (group II). CONCLUSION: The results indicate that the CO could prevent CVDs via suppressing oxidative stress, ameliorating inflammation and apoptosis in hyperlipidemic rats.

scholarly journals Sulforaphane Protect Against Cadmium-Induced Oxidative Damage in mouse Leydigs cells by Activating Nrf2/ARE Signaling Pathway

2019 ◽  
Vol 20 (3) ◽  
pp. 630 ◽  
Author(s):  
Shu-Hua Yang ◽  
Peng Li ◽  
Li-Hui Yu ◽  
Lin Li ◽  
Miao Long ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Antioxidant Response ◽  
Enzyme Linked Immunosorbent Assay ◽  
Related Factor ◽  
Expression Of Genes ◽  
Glutamylcysteine Synthetase ◽  
Polymerase Chain

Cadmium (Cd) is harmful for humans and animals, especially for the reproductive system. However, the mechanism of its toxicity has not been elucidated, and how to alleviate its toxicity is very important. This study aimed to explore the role and mechanism of action of sulforaphane (SFN) in protecting mouse Leydigs (TM3) cells from cadmium (Cd)-induced damage. The half-maximal inhibitory concentration (IC50) of Cd and the safe doses of SFN were determined using a methyl thiazolyl tetrazolium (MTT) assay. The testosterone secretion from TM3 cells was measured using the enzyme-linked immunosorbent assay. The intracellular oxidative stress was evaluated using corresponding kits. The cell apoptosis was detected using flow cytometry. The mRNA expression of genes associated with NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling was detected using reverse transcription–polymerase chain reaction, including Nrf2, heme oxygenase I (HO-1), glutathione peroxidase (GSH-Px), NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1), and γ-glutamylcysteine synthetase (γ-GCS). The protein expression of Nrf2, GSH-Px, HO-1, γ-GCS, and NQO1 was detected using Western blot analysis. The results showed that the IC50 of Cd to TM3 cells was 51.4 µmol/L. SFN reduced the release of lactate dehydrogenase from Cd-exposed cells. Cd + SFN 2.5 treatment significantly elevated testosterone concentration compared with the Cd group (p < 0.05). SFN significantly increased total superoxide dismutase (T-SOD) and GSH-Px activity and GSH content in Cd-treated cells (p < 0.05; p < 0.01), inhibited the production of malondialdehyde or reactive oxygen species caused by Cd (p < 0.05; p < 0.01), and reduced the apoptotic rate of Cd-induced TM3 cells (p < 0.01). SFN upregulated the mRNA expression of Nrf2, GSH-Px, HO-1, NQO1, and γ-GCS in Cd-treated cells, indicating the protective effect of SFN against Cd-induced oxidative stress or cell apoptosis by activating the Nrf2/ARE signaling pathway.

scholarly journals Analysis of the Oxidative Stress Status in Nonspecific Vaginitis and Its Role in Vaginal Epithelial Cells Apoptosis

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Zhaojie Chen ◽  
Zhen Zhang ◽  
Haiyan Zhang ◽  
Beibei Xie
Keyword(s):  
Oxidative Stress ◽  
Cell Apoptosis ◽  
Mitochondrial Pathway ◽  
Vaginal Mucosa ◽  
Vaginal Epithelial Cells ◽  
Oxidative Stress Status ◽  
Epithelial Cell Apoptosis ◽  
Vaginal Tract ◽  
Reactive Oxidant

Nonspecific vaginitis (NSV), also named bacterial vaginosis, is one of the most common genital system diseases in women during their reproductive years. The specific pathogenic mechanism of NSV is not clear yet. Upon the balance alteration, large amount of reactive oxidant species (ROS) is generated and accumulated in the genital tract, and thus resulting in oxidative stress, which has been reported to be an important trigger of mitochondrial pathway cell apoptosis. In this study, the antioxidant secretion level and antioxidant enzyme activity in the vaginal discharge were evaluated to analyze the oxidative status in the vaginal tract of NSV patients. The effect of oxidative stress on the vaginal mucosa epithelial cell apoptosis was then studied. The role of oxidative stress on NSV development was uncovered; thus open new direction for the prevention and treatment of NSV by providing antiradical agents was revealed.

scholarly journals Metformin prevents methylglyoxal-induced apoptosis by suppressing oxidative stress in vitro and in vivo

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Gang Wang ◽  
Yanan Wang ◽  
Qinzhi Yang ◽  
Chunrong Xu ◽  
Youkun Zheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Apoptosis ◽  
Vascular Complications ◽  
Tunel Staining ◽  
Ros Generation ◽  
Dependent Manner ◽  
Diabetic Vascular Complications ◽  
Induced Apoptosis

AbstractMethylglyoxal (MGO) is an active metabolite of glucose and plays a prominent role in the pathogenesis of diabetic vascular complications, including endothelial cell apoptosis induced by oxidative stress. Metformin (MET), a widely prescribed antidiabetic agent, appears to reduce excessive reactive oxygen species (ROS) generation and limit cell apoptosis. However, the molecular mechanisms underlying this process are still not fully elucidated. We reported here that MET prevents MGO-induced apoptosis by suppressing oxidative stress in vitro and in vivo. Protein expression and protein phosphorylation were investigated using western blotting, ELISA, and immunohistochemical staining, respectively. Cell viability and apoptosis were assessed by the MTT assay, TUNEL staining, and Annexin V-FITC and propidium iodide double staining. ROS generation and mitochondrial membrane potential (MMP) were measured with fluorescent probes. Our results revealed that MET prevented MGO-induced HUVEC apoptosis, inhibited apoptosis-associated biochemical changes such as loss of MMP, the elevation of the Bax/Bcl-2 ratio, and activation of cleaved caspase-3, and attenuated MGO-induced mitochondrial morphological alterations in a dose-dependent manner. MET pretreatment also significantly suppressed MGO-stimulated ROS production, increased signaling through the ROS-mediated PI3K/Akt and Nrf2/HO-1 pathways, and markedly elevated the levels of its downstream antioxidants. Finally, similar results were obtained in vivo, and we demonstrated that MET prevented MGO-induced oxidative damage, apoptosis, and inflammation. As expected, MET reversed MGO-induced downregulation of Nrf2 and p-Akt. In addition, a PI3K inhibitor (LY-294002) and a Nrf2 inhibitor (ML385) observably attenuated the protective effects of MET on MGO-induced apoptosis and ROS generation by inhibiting the Nrf2/HO-1 pathways, while a ROS scavenger (NAC) and a permeability transition pores inhibitor (CsA) completely reversed these effects. Collectively, these findings broaden our understanding of the mechanism by which MET regulates apoptosis induced by MGO under oxidative stress conditions, with important implications regarding the potential application of MET for the treatment of diabetic vascular complications.

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