l-Arginine Alleviates LPS-Induced Oxidative Stress and Apoptosis via Activating SIRT1-AKT-Nrf2 and SIRT1-FOXO3a Signaling Pathways in C2C12 Myotube Cells

l-arginine (l-Arg) has been reported to possess a wide range of functions, including anti-inflammatory, anti-oxidative, and anti-apoptosis. However, the role of l-Arg in LPS-induced muscle injury and its potential protective mechanism has not been well elucidated. This study aimed to investigate the effects of l-Arg on the LPS-induced oxidative stress and apoptosis in differentiated C2C12 myotube cells. Our results demonstrated that myotube cells treated with 0.2 mg/mL LPS significantly decreased cell viability. l-Arg treatment significantly suppressed LPS induced ROS accumulation and cell apoptosis. Furthermore, l-Arg improved antioxidant-related enzymes’ activities; increased antioxidant ability via Akt-Nrf2 signaling pathway; maintained the mitochondrial membrane potential (MMP); and enhanced FOXO3a expression, leading to a decrease in the mitochondrial-associated apoptotic proteins. In addition, l-Arg exposure dramatically increased the mRNA and protein expressions of SIRT1. The cytoprotective effect of l-Arg was restricted by the SIRT1 inhibitor EX527, which led to an increase in ROS level, apoptosis rate, and decreased cell MMP. The results also demonstrated that EX527 treatment significantly eliminated the effect of l-Arg on LPS-induced oxidative damage and mitochondria-mediated cell apoptosis. Our findings revealed that l-Arg could be used as a potential nutraceutical in reducing muscle injury via regulating SIRT1-Akt-Nrf2 and SIRT1-FOXO3a-mitochondria apoptosis signaling pathways.

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L-Arginine Alleviates LPS-induced Oxidative Stress and Apoptosis via Activating SIRT1-AKT-Nrf2 and SIRT1-FOXO3a Signaling Pathways in C2C12 Myotube Cells

10.21203/rs.3.rs-1045345/v1 ◽

2021 ◽

Author(s):

Ye Zhao ◽

Qin Jiang ◽

Xuefei Zhang ◽

Xiaoxiao Zhu ◽

Xia Dong ◽

...

Keyword(s):

Oxidative Stress ◽

Signaling Pathways ◽

Cell Apoptosis ◽

Muscle Injury ◽

In Vitro Models ◽

Protective Mechanism ◽

Nrf2 Signaling Pathway ◽

Wide Range ◽

C2c12 Myotube

Abstract BackgroundAs a highly plasticized tissue, muscle could exert a spontaneous immune behavior in response to external pathogen stimulation. L-arginine (L-Arg) has been reported to possess a wide range of functions, including anti-inflammatory, anti-oxidative, and anti-apoptosis. However, the role of L-Arg in LPS-induced muscle injury and its potential protective mechanism has not been well elucidated. This study aimed to investigate the effects of L-Arg on the LPS-induced oxidative stress and apoptosis in vitro models of well-differentiated C2C12 myotube cells. ResultsIn the present study, we first demonstrated that myotube cells treated with 0.2 mg/mL lipopolysaccharide (LPS) significantly decreased cell viability. Then, different concentrations of L-Arg (0, 0.5, 2.5, 5 mM)-pretreated myotube cells were exposed to LPS. The results showed that L-Arg treatment significantly suppressed reactive oxygen species (ROS) accumulation and cell apoptosis. Furthermore, L-Arg improved antioxidant-related enzymes’ activities; increased antioxidant ability via Akt-Nrf2 signaling pathway; maintained the mitochondrial membrane potential (MMP) and enhanced forkhead box protein 3a (FOXO3a) expression, lead to a decrease in the mitochondrial-associated apoptotic proteins. In addition, L-Arg exposure dramatically increased the mRNA and protein expressions of Sirtuin1 (SIRT1). The cytoprotective effect of L-Arg was restricted by the SIRT1 inhibitor EX527, which led to an increase in ROS level, apoptosis rate, and decreased cell MMP. The results also demonstrated that EX527 treatment significantly eliminated the effect of L-Arg on LPS-induced oxidative damage and mitochondria-mediated cell apoptosis. ConclusionsOur findings revealed that L-Arg could be used as a potential nutraceutical in reducing muscle injury via regulating SIRT1-Akt-Nrf2 and SIRT1-FOXO3a-mitochondria apoptosis signaling pathways.

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Cyclosporin A protects JEG-3 cells against oxidative stress-induced apoptosis by inhibiting the p53 and JNK/p38 signaling pathways

Reproductive Biology and Endocrinology ◽

10.1186/s12958-020-00658-0 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Bin He ◽

Qi Yue Li ◽

Yuan Yuan Wu ◽

Jing Ling Ruan ◽

Xiao Ming Teng ◽

...

Keyword(s):

Oxidative Stress ◽

Cyclosporin A ◽

Signaling Pathways ◽

Western Blotting ◽

Cell Apoptosis ◽

Caspase 3 ◽

B Cell Lymphoma ◽

Trophoblast Invasion ◽

Trophoblast Cells ◽

Induced Apoptosis

Abstract Background Trophoblast cells are required for the establishment of pregnancy and fetal development. Apoptosis is an essential feature for trophoblast invasion. Uncontrolled trophoblast apoptosis is related to some complicate pregnancies. Oxidative stress (OS) is an important inducer of trophoblast apoptosis. Cyclosporin A (CsA) has been shown to promote the activity of trophoblast cells and reduce OS-induced oxidative injury. We investigated the role and mechanism of CsA in oxidative stress-induced trophoblast cell apoptosis. Methods JEG-3 cells were cocultured with H2O2 and CsA. Cell viability and morphology were measured by MTT assay and DAPI staining. Cell apoptosis was tested with annexin V/PI staining. The expression of Bcl-2-associated X protein (Bax), B-cell lymphoma/leukemia-2 (Bcl-2), cleaved poly (ADP-ribose) polymerase (PARP) and pro-caspase-3 was assayed by western blotting. The protein expression and phosphorylation of p53 and mitogen-activated protein kinase (MAPK) kinases (JNK, ERK1/2 and p38) were examined by western blotting. Results CsA increased the viability, alleviated morphological injury and reduced cell apoptosis of the H2O2-treated JEG-3 cells. CsA also attenuated the activation of p53, decreased the expression of Bax and cleavage of PARP, and increased the expression of Bcl-2 and pro-caspase-3 in the JEG-3 treated with H2O2. Furthermore, CsA reduced the activation of JNK and P38 but had no significant effect on the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the H2O2-treated JEG-3 cells. Promoting the activation of JNK and p38 impaired the protective effect of CsA on OS-induced trophoblast apoptosis. Conclusions These results suggested that CsA protected trophoblast cells from OS-induced apoptosis via the inhibition of the p53 and JNK/p38 signaling pathways.

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Naoxintong/PPARαSignaling Inhibits H9c2 Cell Apoptosis and Autophagy in Response to Oxidative Stress

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/4370381 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Huimin Xu ◽

Jianhua Jin ◽

Lu Chen ◽

Chunxiao Li ◽

Qinggang Xu ◽

...

Keyword(s):

Oxidative Stress ◽

Flow Cytometry ◽

Chinese Medicine ◽

Cardiovascular Diseases ◽

Protective Effect ◽

Cell Apoptosis ◽

H9c2 Cell ◽

Protective Mechanism ◽

H9c2 Cells ◽

Protein Levels

Naoxintong (NXT) is an empirical formula based on the principle of traditional Chinese medicine, which has been approved by China Food and Drug Administration (CFDA) and is widely used for treatment of patients with cerebrovascular and cardiovascular diseases in China. The aim of this study is to investigate the protective mechanism of NXT on H9c2 cells (cardiogenic cell line) in response to H2O2. MTT, Western blot, and flow cytometry (FCM) methods were used to identify the protective effect of NXT extract on H2O2-induced H9c2 cells. Here we found that NXT extract significantly increased H9c2 cell viability and reduced H2O2-induced cell apoptosis and autophagy. More importantly, NXT inhibited H2O2-induced H9c2 cell apoptosis and autophagy by increasing PPARαprotein levels. In contrast, silenced PPARαterminated NXT protective effect on H2O2-induced H9c2 cells. These findings suggest that NXT/PPARαsignaling suppressed H2O2-induced H9c2 cell apoptosis and autophagy.

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Alginate Oligosaccharide Ameliorates D-Galactose-Induced Kidney Aging in Mice through Activation of the Nrf2 Signaling Pathway

BioMed Research International ◽

10.1155/2021/6623328 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Hui Pan ◽

Wenjing Feng ◽

Ming Chen ◽

Hong Luan ◽

Yi Hu ◽

...

Keyword(s):

Oxidative Stress ◽

Signaling Pathway ◽

Aging Process ◽

Molecular Mechanisms ◽

Nuclear Translocation ◽

Heme Oxygenase 1 ◽

Quinone Oxidoreductase ◽

Nrf2 Signaling Pathway ◽

Wide Range ◽

Alginate Oligosaccharide

Aging is an independent risk factor for the development of age-related progressive kidney injury. As a part of the aging process, kidney aging has been indicated to be associated with oxidative stress-induced damage. Ameliorating oxidative damage is therefore considered a promising strategy for delaying kidney aging. Alginate oligosaccharide (AOS) has been reported to have a wide range of biological and pharmacological activities. However, no studies have focused on the role of AOS in delaying the kidney aging process. In this study, we aimed to evaluate the potential effects of AOS on kidney aging and its possible mechanisms. Subcutaneous injection of D-galactose (D-gal) (200 mg·kg-1·d-1) in C57BL/6J mice for 8 weeks was used to establish the aging model. AOS (200 mg·kg-1·d-1) was administered via oral gavage for the last four weeks. As a result, AOS inhibited the D-gal-induced upregulation of aging markers and significantly improved the kidney index and kidney function of D-gal-induced mice. In addition, AOS ameliorated the degree of tissue damage and fibrosis in the aging kidney. To further explore the potential mechanisms by which AOS attenuates the kidney aging process, the associated oxidative stress-induced damage was analyzed in depth. The data showed that AOS upregulated the expression of Klotho and decreased malondialdehyde levels by increasing the expression of antioxidant enzymes. Furthermore, our results suggested that AOS activated the nuclear factor erythrogen-2 associated factor 2 (Nrf2) pathway by promoting Nrf2 nuclear translocation in aging mice and upregulated the downstream expression of heme oxygenase-1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO1). In conclusion, the present study demonstrated that AOS is a promising agent for attenuating kidney aging, and the underlying molecular mechanisms are related to the activation of the Nrf2 signaling pathway.

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Lifestyle-specific S-nitrosylation of protein cysteine thiols regulates Escherichia coli biofilm formation and resistance to oxidative stress

npj Biofilms and Microbiomes ◽

10.1038/s41522-021-00203-w ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Nicolas Barraud ◽

Sylvie Létoffé ◽

Christophe Beloin ◽

Joelle Vinh ◽

Giovanni Chiappetta ◽

...

Keyword(s):

Oxidative Stress ◽

Escherichia Coli ◽

Redox Homeostasis ◽

Acid Synthesis ◽

Amino Acid Synthesis ◽

Physiological Basis ◽

Proteomic Approach ◽

Wide Range ◽

Range Of Functions ◽

Cysteine Thiols

AbstractCommunities of bacteria called biofilms are characterized by reduced diffusion, steep oxygen, and redox gradients and specific properties compared to individualized planktonic bacteria. In this study, we investigated whether signaling via nitrosylation of protein cysteine thiols (S-nitrosylation), regulating a wide range of functions in eukaryotes, could also specifically occur in biofilms and contribute to bacterial adaptation to this widespread lifestyle. We used a redox proteomic approach to compare cysteine S-nitrosylation in aerobic and anaerobic biofilm and planktonic Escherichia coli cultures and we identified proteins with biofilm-specific S-nitrosylation status. Using bacterial genetics and various phenotypic screens, we showed that impairing S-nitrosylation in proteins involved in redox homeostasis and amino acid synthesis such as OxyR, KatG, and GltD altered important biofilm properties, including motility, biofilm maturation, or resistance to oxidative stress. Our study therefore revealed that S-nitrosylation constitutes a physiological basis underlying functions critical for E. coli adaptation to the biofilm environment.

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Protective Mechanism of Humanin Against Oxidative Stress in Aging-Related Cardiovascular Diseases

Frontiers in Endocrinology ◽

10.3389/fendo.2021.683151 ◽

2021 ◽

Vol 12 ◽

Author(s):

He Cai ◽

Yunxia Liu ◽

Hongbo Men ◽

Yang Zheng

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Cardiovascular Diseases ◽

Protein Kinase ◽

Signaling Pathways ◽

Dynamic Balance ◽

Janus Kinase ◽

Protective Mechanism ◽

Related Factor ◽

The Relationship

Physiological reactive oxygen species (ROS) are important regulators of intercellular signal transduction. Oxidative and antioxidation systems maintain a dynamic balance under physiological conditions. Increases in ROS levels destroy the dynamic balance, leading to oxidative stress damage. Oxidative stress is involved in the pathogenesis of aging-related cardiovascular diseases (ACVD), such as atherosclerosis, myocardial infarction, and heart failure, by contributing to apoptosis, hypertrophy, and fibrosis. Oxidative phosphorylation in mitochondria is the main source of ROS. Increasing evidence demonstrates the relationship between ACVD and humanin (HN), an endogenous peptide encoded by mitochondrial DNA. HN protects cardiomyocytes, endothelial cells, and fibroblasts from oxidative stress, highlighting its protective role in atherosclerosis, ischemia–reperfusion injury, and heart failure. Herein, we reviewed the signaling pathways associated with the HN effects on redox signals, including Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2), chaperone-mediated autophagy (CMA), c-jun NH2 terminal kinase (JNK)/p38 mitogen-activated protein kinase (p38 MAPK), adenosine monophosphate-activated protein kinase (AMPK), and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)-Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3). Furthermore, we discussed the relationship among HN, redox signaling pathways, and ACVD. Finally, we propose that HN may be a candidate drug for ACVD.

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Troxerutin Reduces Kidney Damage against BDE-47-Induced Apoptosis via Inhibiting NOX2 Activity and Increasing Nrf2 Activity

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/6034692 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 14

Author(s):

Qun Shan ◽

Juan Zhuang ◽

Guihong Zheng ◽

Zifeng Zhang ◽

Yanqiu Zhang ◽

...

Keyword(s):

Cell Apoptosis ◽

Underlying Mechanism ◽

Protective Mechanism ◽

Oxygen Species ◽

Pathological Mechanism ◽

Nrf2 Signaling Pathway ◽

Induced Apoptosis ◽

Oxidant Status ◽

Anti Inflammation

2,2,4,4-Tetrabromodiphenyl ether (BDE-47), one of the persistent organic pollutants, seriously influences the quality of life; however, its pathological mechanism remains unclear. Troxerutin is a flavonoid with pharmacological activity of antioxidation and anti-inflammation. In the present study, we investigated troxerutin against BDE-47-induced kidney cell apoptosis and explored the underlying mechanism. The results show that troxerutin reduced renal cell apoptosis and urinary protein secretion in BDE-47-treated mice. Western blot analysis shows that troxerutin supplement enhanced the ratio of Bcl-2/Bax; inhibited the release of cytochrome c from mitochondria, the activation of procaspase-9 and procaspase-3, and the cleavage of PARP; and reduced FAS, FASL, and caspase-8 levels induced by BDE-47. In addition, troxerutin decreased the production of reactive oxygen species (ROS) and increased the activities of antioxidative enzymes. Furthermore, troxerutin blunted Nrf2 ubiquitylation, enhanced the activity of Nrf2, decreased the activity of NOX2, and ameliorated kidney oxidant status of BDE-47-treated mice. Together, these results confirm that troxerutin could alleviate the cytotoxicity of BDE-47 through antioxidation and antiapoptosis, which suggests that its protective mechanism is involved in the inhibition of apoptosis via suppressing NOX2 activity and increasing Nrf2 signaling pathway.

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Lifestyle-specific S-nitrosylation of protein cysteine thiols regulates Escherichia coli biofilm formation and resistance to oxidative stress

10.1101/2020.09.29.318139 ◽

2020 ◽

Author(s):

Nicolas Barraud ◽

Sylvie Létoffé ◽

Christophe Beloin ◽

Joelle Vinh ◽

Giovanni Chiappetta ◽

...

Keyword(s):

Oxidative Stress ◽

Escherichia Coli ◽

Redox Homeostasis ◽

Acid Synthesis ◽

Amino Acid Synthesis ◽

Physiological Basis ◽

Proteomic Approach ◽

Wide Range ◽

Range Of Functions ◽

Cysteine Thiols

SUMMARYCommunities of bacteria called biofilms are characterized by reduced diffusion, steep oxygen and redox gradients and specific properties compared to individualized planktonic bacteria. In this study, we investigated whether signaling via nitrosylation of protein cysteine thiols (S-nitrosylation), regulating a wide range of functions in eukaryotes, could also specifically occur in biofilms and contribute to bacterial adaptation to this widespread lifestyle. We used a redox proteomic approach to compare cysteine S-nitrosylation in aerobic and anaerobic biofilm and planktonic Escherichia coli cultures and we identified proteins with biofilm-specific S-nitrosylation status. Using bacterial genetics and various phenotypic screens, we showed that impairing S-nitrosylation in proteins involved in redox homeostasis and amino acid synthesis such as OxyR, KatG and GltD altered important biofilm properties, including motility, biofilm maturation or resistance to oxidative stress. Our study therefore revealed that S-nitrosylation constitutes a physiological basis underlying functions critical for E. coli adaptation to the biofilm environment.

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Neuregulin-1β Protects the Rat Diaphragm during Sepsis against Oxidative Stress and Inflammation by Activating the PI3K/Akt Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/1720961 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Hua Liu ◽

Xiao-jian Weng ◽

Jun-yan Yao ◽

Jun Zheng ◽

Xiang Lv ◽

...

Keyword(s):

Oxidative Stress ◽

Proinflammatory Cytokines ◽

Cell Apoptosis ◽

Proinflammatory Cytokine ◽

Ache Activity ◽

Muscle Injury ◽

Akt Signaling ◽

Tunel Staining ◽

Ros Production ◽

Diaphragm Dysfunction

Sepsis-induced diaphragm dysfunction (SIDD) which is mainly characterized by decrease in diaphragmatic contractility has been identified to cause great harms to patients. Therefore, there is an important and pressing need to find effective treatments for improving SIDD. In addition, acetylcholinesterase (AChE) activity is a vital property of the diaphragm, so we evaluated both diaphragmatic contractility and AChE activity. Though neuregulin-1β (NRG-1β) is known to exert organ-protective effects in some inflammatory diseases, little is known about the potential of NRG-1β therapy in the diaphragm during sepsis. Our study was aimed at exploring the effects of NRG-1β application on diaphragmatic contractility and AChE activity during sepsis. Proinflammatory cytokines, muscle injury biomarkers in serum, contractile force, AChE activity, proinflammatory cytokines, oxidative parameters, histological condition, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and expression of phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB/Akt) signaling proteins in the diaphragm were measured and compared between nonseptic and septic groups with or without NRG-1β treatment. In vitro, the effects of NRG-1β on reactive oxygen species (ROS) production in the lipopolysaccharide- (LPS-) stimulated L6 rat muscle skeletal cells with or without the Akt inhibitor MK-2206 were detected. NRG-1β inhibited proinflammatory cytokine release and muscle injury biomarkers soaring in serum and improved the sepsis-induced diaphragm dysfunction and AChE activity decrease significantly during sepsis. Meanwhile, the inflammatory response, oxidative stress, pathological impairment, and cell apoptosis in the diaphragm were mitigated by NRG-1β. And NRG-1β activated the PI3K/Akt signaling in the diaphragm of septic rats. Elevated ROS production in the LPS-stimulated L6 rat skeletal muscle cells was reduced after treatment with NRG-1β, while MK-2206 blocked these effects of NRG-1β. In conclusion, our findings underlined that NRG-1β could reduce circulating levels of proinflammatory cytokines in rats with sepsis, adjust diaphragmatic proinflammatory cytokine level, mitigate diaphragmatic oxidative injury, and lessen diaphragm cell apoptosis, thereby improving diaphragmatic function, and play a role in diaphragmatic protection by activating PI3K/Akt signaling.

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Alfalfa saponins plays protective roles in oxidative stress-induced apoptotic cells

10.21203/rs.3.rs-40613/v1 ◽

2020 ◽

Author(s):

Yalei Cui ◽

Boshuai Liu ◽

Xiao Sun ◽

Zidan Li ◽

Yanyan Chen ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Apoptosis ◽

Mapk Signaling ◽

Feed Additive ◽

Drug Candidate ◽

Protective Mechanism ◽

Intestinal Epithelial ◽

Study Results ◽

New Strategy ◽

Antioxidant Effects

Abstract Background: As is known, alfalfa saponin can be used as a feed additive in the pig’s diet. And the addition of alfalfa saponin to the pig’s diet could improve animal antioxidant capacity. However, the mechanism by which alfalfa saponins exerts their antioxidant effects has not been studied. To address this issue, H2O2-induced rat intestinal epithelial cell was used to explore the protective mechanism of alfalfa saponins in this study. Results: Alfalfa saponin could rescue the cell proliferation activity, elevate the amount of antioxidant enzymes and downregulate the release of MDA and LDH in H2O2-induced cells. The results indicated that the antioxidant activity of alfalfa saponin was achieved by restoring GSH homeostasis. Further results demonstrated that alfalfa saponin could inhibit cell apoptosis through activating MAPK signaling pathway. Conclusions: The mechanism by which alfalfa saponins exerts their antioxidant effects was elucidated. Therefore, alfalfa saponin could function as cellular oxidative damage inhibitor, green feed additive or potential drug candidate, providing new strategy for inhibiting cell apoptosis induced by oxidative stress in monogastric animals.

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