Enhanced survival effect of pyruvate correlates MAPK and NF-κB activation in hydrogen peroxide-treated human endothelial cells

2004 ◽  
Vol 96 (2) ◽  
pp. 793-801 ◽  
Author(s):  
Yong-Jin Lee ◽  
Il-Jun Kang ◽  
Rolf Bünger ◽  
Young-Hee Kang
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Therapeutic Potential ◽  
Cell Model ◽  
Mapk Pathway ◽  
Umbilical Vein ◽  
Reactive Oxygen ◽  
Antioxidant Potential ◽  
Mitogen Activated Protein Kinase ◽  
Oxygen Species

We recently reported that pyruvate inhibited translocation and activation of p53 caused by DNA damage due to oxidant injury (Lee YJ, Kang IJ, Bünger R, and Kang YH. Microvasc Res 66: 91-101, 2003); this was associated with increased expression of apoptosis-related bcl-2 and decreased expression of bax gene. This study attempted to delineate possible regulatory sites and mechanisms of antiapoptotic pyruvate, focusing on reactive oxygen species-mediated signaling in a human umbilical vein endothelial cell model. We compared the effects of the cytosolic reductant l-lactate and malate-aspartate shuttle blocker aminooxyacetate, both of which increase cytosolic NADH, on the downstream signaling pathway. Hydrogen peroxide (0.5 mM H2O2) depleted intracellular total glutathione that was prevented by pyruvate but not by l-lactate or aminooxyacetate. Activation of caspase-3 and the cleavage of procaspase-6 and procaspase-7 were strongly inhibited by pyruvate but markedly enhanced by l-lactate and aminooxyacetate, implicating redox-related antiapoptotic mechanisms of pyruvate. Western blot analysis and immunochemical data revealed that H2O2-induced transactivation of nuclear factor-κB (NF-κB) was also inhibited by pyruvate but not by l-lactate or aminooxyacetate. In addition, H2O2 downregulated extracellular signal-regulated kinase (ERK1/2) and phosphorylated p38 mitogen-activated protein kinase (MAPK), effects that were fully reversed by pyruvate within 2 h. Collectively, these findings indicate that pyruvate can protect cellular glutathione, thus enhancing cellular antioxidant potential, and that enhanced antioxidant potential can desensitize NF-κB transactivation due to reactive oxygen species, suggesting possible metabolic redox relations to NF-κB. Furthermore, pyruvate blocked the p38 MAPK pathway and activated the ERK pathway in an apparently redox-sensitive manner, which may regulate expression of genes believed to prevent apoptosis and promote cell survival. Thus pyruvate may have therapeutic potential for reducing endothelial dysfunction and improving survival during oxidative stress.

scholarly journals Guilingji Protects Against Spermatogenesis Dysfunction From Oxidative Stress via Regulation of MAPK and Apoptotic Signaling Pathways in Immp2l Mutant Mice

2022 ◽  
Vol 12 ◽  
Author(s):  
Zhenqing Wang ◽  
Yun Xie ◽  
Haicheng Chen ◽  
Jiahui Yao ◽  
Linyan Lv ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Male Infertility ◽  
Mapk Pathway ◽  
Reactive Oxygen ◽  
Mutant Mice ◽  
Mitogen Activated Protein Kinase ◽  
Seminiferous Tubules ◽  
Oxygen Species ◽  
Inner Mitochondrial Membrane

Male infertility is a major health issue with an estimated prevalence of 4.2% of male infertility worldwide. Oxidative stress (OS) is one of the main causes of male infertility, which is characterized by excessive reactive oxygen species (ROS) or lack of antioxidants. Meanwhile, it is reported that oxidative stress plays an important role in the spermatogenic impairment in Inner mitochondrial membrane peptidase 2-like (Immp2l) mutant mice. In this study, we focused on the potential mechanism of Guilingji in protecting the spermatogenic functions in Immp2l mutant mice. The results revealed that Immp2l mutant mice exhibit impaired spermatogenesis and histology shows seminiferous tubules with reduced spermatogenic cells. After administration of Guilingji [150 mg/kg per day intragastric gavage], however, alleviated spermatogenesis impairment and reversed testis histopathological damage and reduced apoptosis. What’s more, western blotting and the levels of redox classic markers revealed that Guilingji can markedly reduce reactive oxygen species. Moreover, Guilingji treatment led to inhibition of the phosphorylation of mitogen-activated protein kinase (MAPK), regulated apoptosis in the cells. In summary, Guilingji can improve spermatogenesis in Immp2l mutant mice by regulating oxidation-antioxidant balance and MAPK pathway. Our data suggests that Guilingji may be a promising and effective antioxidant candidate for the treatment of male infertility.

scholarly journals 5-Hydroxytryptamine1A receptor/Giβγ stimulates mitogen-activated protein kinase via NAD(P)H oxidase and reactive oxygen species upstream of Src in Chinese hamster ovary fibroblasts

2000 ◽  
Vol 347 (1) ◽  
pp. 61-67 ◽  
Author(s):  
Yurii V. MUKHIN ◽  
Maria N. GARNOVSKAYA ◽  
Georgiann COLLINSWORTH ◽  
Jasjit S. GREWAL ◽  
DeKisha PENDERGRASS ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Chinese Hamster Ovary ◽  
Cho Cells ◽  
Chinese Hamster ◽  
Reactive Oxygen ◽  
Mitogen Activated Protein Kinase ◽  
Oxygen Species ◽  
Erk Activation ◽  
Activation Pathway

The hypothesis of this work is that the ‘serotonin’ or 5-hydroxytryptamine (5-HT)1A receptor, which activates the extracellular signal-regulated kinase (ERK) through a Giβγ-mediated pathway, does so through the intermediate actions of reactive oxygen species (ROS). Five criteria were shown to support a key role for ROS in the activation of ERK by the 5-HT1A receptor. (1) Antioxidants inhibit activation of ERK by 5-HT. (2) Application of cysteine-reactive oxidant molecules activates ERK. (3) The 5-HT1A receptor alters cellular redox properties, and generates both superoxide and hydrogen peroxide. (4) A specific ROS-producing enzyme [NAD(P)H oxidase] is involved in the activation of ERK. (5) There is specificity both in the effects of various chemical oxidizers, and in the putative location of the ROS in the ERK activation pathway. We propose that NAD(P)H oxidase is located in the ERK activation pathway stimulated by the transfected 5-HT1A receptor in Chinese hamster ovary (CHO) cells downstream of Giβγ subunits and upstream of or at the level of the non-receptor tyrosine kinase, Src. Moreover, these experiments provide confirmation that the transfected human 5-HT1A receptor induces the production of ROS (superoxide and hydrogen peroxide) in CHO cells, and support the possibility that an NAD(P)H oxidase-like enzyme might be involved in the 5-HT-mediated generation of both superoxide and hydrogen peroxide.

scholarly journals Parkia speciosa Hassk. Empty Pod Extract Alleviates Angiotensin II-Induced Cardiomyocyte Hypertrophy in H9c2 Cells by Modulating the Ang II/ROS/NO Axis and MAPK Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Hawa Nordin Siti ◽  
Juriyati Jalil ◽  
Ahmad Yusof Asmadi ◽  
Yusof Kamisah
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Angiotensin Ii ◽  
Mapk Pathway ◽  
Reactive Oxygen ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Cardiomyocyte Hypertrophy ◽  
Oxygen Species ◽  
Ang Ii

Cardiac hypertrophy is characteristic of heart failure in patients who have experienced cardiac remodeling. Many medicinal plants, including Parkia speciosa Hassk., have documented cardioprotective effects against such pathologies. This study investigated the activity of P. speciosa empty pod extract against cardiomyocyte hypertrophy in H9c2 cardiomyocytes exposed to angiotensin II (Ang II). In particular, its role in modulating the Ang II/reactive oxygen species/nitric oxide (Ang II/ROS/NO) axis and mitogen-activated protein kinase (MAPK) pathway was examined. Treatment with the extract (12.5, 25, and 50 μg/ml) prevented Ang II-induced increases in cell size, NADPH oxidase activity, B-type natriuretic peptide levels, and reactive oxygen species and reductions in superoxide dismutase activity. These were comparable to the effects of the valsartan positive control. However, the extract did not significantly ameliorate the effects of Ang II on inducible nitric oxide synthase activity and nitric oxide levels, while valsartan did confer such protection. Although the extract decreased the levels of phosphorylated extracellular signal-related kinase, p38, and c-Jun N-terminal kinase, valsartan only decreased phosphorylated c-Jun N-terminal kinase expression. Phytochemical screening identified the flavonoids rutin (1) and quercetin (2) in the extract. These findings suggest that P. speciosa empty pod extract protects against Ang II-induced cardiomyocyte hypertrophy, possibly by modulating the Ang II/ROS/NO axis and MAPK signaling pathway via a mechanism distinct from valsartan.

Reactive oxygen species (H2O2): effects on the gallbladder muscle of guinea pigs

2002 ◽  
Vol 282 (2) ◽  
pp. G300-G306 ◽  
Author(s):  
Zuo-Liang Xiao ◽  
Maria J. Pozo Andrada ◽  
Piero Biancani ◽  
Jose Behar
Keyword(s):  
Reactive Oxygen Species ◽  
Protein Kinase ◽  
Mapk Pathway ◽  
Binding Capacity ◽  
Reactive Oxygen ◽  
Membrane Receptors ◽  
Mitogen Activated Protein Kinase ◽  
Radical Scavenger ◽  
Oxygen Species

Reactive oxygen species (ROS) have been implicated in the pathogenesis of muscle dysfunction in acute inflammatory processes. The aim of these studies was to determine the effects of ROS on gallbladder muscle function in vitro. Single muscle cells were obtained by enzymatic digestion. H2O2 (70 μM) caused maximal contraction of up to 14% and blocked the response to CCK-8, ACh, and KCl. It did not affect the contractions induced by guanosine 5′- O-(3-thiotriphosphate), diacylglycerol, and inositol 1,4,5-trisphosphate that circumvent membrane receptors. The contraction induced by H2O2 was inhibited by AACOCF3 [cytosolic phospholipase A2(cPLA2) inhibitor], indomethacin (cyclooxygenase inhibitor), chelerythrine [protein kinase C (PKC) inhibitor], or PD-98059 [mitogen-activated protein kinase (MAPK) inhibitor]. H2O2 also reduced the CCK receptor binding capacity from 0.36 ± 0.05 pmol/mg protein (controls) to 0.17 ± 0.03 pmol/mg protein. The level of lipid peroxidation as well as the PGE2 content was significantly increased after H2O2 pretreatment. Unlike superoxide dismutase, the free radical scavenger catalase prevented the H2O2 induced contraction, and its inhibition of the CCK-8 induced contraction. It is concluded that ROS cause damage to the plasma membrane of the gallbladder muscle and contraction through the generation of PGE2 induced by cPLA2-cyclooxygenase and probably mediated by the PKC-MAPK pathway.

scholarly journals Apoptosis Induction by the Total Flavonoids fromArachniodes exilisin HepG2 Cells through Reactive Oxygen Species-Mediated Mitochondrial Dysfunction Involving MAPK Activation

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Huimin Li ◽  
Jing Chen ◽  
Chaomei Xiong ◽  
Han Wei ◽  
Changchang Yin ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Mitochondrial Dysfunction ◽  
Hepg2 Cells ◽  
Mapk Pathway ◽  
Reactive Oxygen ◽  
Mitogen Activated Protein Kinase ◽  
Total Flavonoids ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Cytochrome C Release

Arachniodes exilisis used as a folk medicine in China and proved to have antibacterial, anti-inflammatory, and sedative activities. In the present study, the antitumor effect of the total flavonoids ofA. exilis(TFAE) against HepG2 cells was evaluated. The results showed that TFAE inhibited the growth of HepG2 cells in a dosage- and time-dependent manner. Flow cytometry and Hoechst 33342 fluorescence staining results showed that TFAE could significantly increase the apoptosis ratio of HepG2 cells, which is accompanied with increased intracellular reactive oxygen species (ROS) production and decreased mitochondrial membrane potential(ΔΨm). Western blotting indicated that TFAE downregulated the ratio of Bcl-2/Bax, increased cytochrome c release, and activated the caspases-3 and -9. Further analysis showed that TFAE stimulated the mitogen-activated protein kinase (MAPK). However, treatment with NAC (reactive oxygen species scavenger) and MAPK-specific inhibitors (SP600125 and SB203580) could reverse the changes of these apoptotic-related proteins. These results suggested that TFAE possessed potential anticancer activity in HepG2 cells through ROS-mediated mitochondrial dysfunction involving MAPK pathway.

Hydrogen peroxide-responsive AIE probe for imaging-guided organelle targeting and photodynamic cancer cell ablation

2021 ◽  
Author(s):  
Qian Wu ◽  
Youmei Li ◽  
Ying Li ◽  
Dong Wang ◽  
Ben Zhong Tang
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Cancer Cell ◽  
Reactive Oxygen ◽  
Living Cells ◽  
Oxygen Species ◽  
Cell Ablation ◽  
Selective Monitoring ◽  
Organelle Targeting

Hydrogen peroxide (H2O2), as one kind of key reactive oxygen species (ROS), is mainly produced endogenously primarily in the mitochondria. The selective monitoring of H2O2 in living cells is of...

scholarly journals Upconversion-based nanosystems for fluorescence sensing of pH and H2O2

2021 ◽  
Author(s):  
Chunning Sun ◽  
Michael Gradzielski
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Excitation Energy ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Fluorescence Sensing ◽  
Living Organisms

Hydrogen peroxide (H2O2), a key reactive oxygen species, plays an important role in living organisms, industrial and environmental fields. Here, a non-contact upconversion nanosystem based on the excitation energy attenuation...

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