Chinese Prescription Kangen-karyu and Salviae Miltiorrhizae Radix Improve Age-Related Oxidative Stress and Inflammatory Response through the PI3K/Akt or MAPK Pathways

2014 ◽  
Vol 42 (04) ◽  
pp. 987-1005 ◽  
Author(s):  
Chan Hum Park ◽  
Dae Hyun Kim ◽  
Min Hi Park ◽  
Mi Kyung Kim ◽  
Nam Deuk Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Salviae Miltiorrhizae ◽  
Mapk Pathways ◽  
Age Related ◽  
Salviae Miltiorrhizae Radix ◽  
Old Rats

This study examined whether Kangen-karyu and its crude drug, Salviae Miltiorrhizae Radix, have a reno-protective effect on the age-related oxidative stress and inflammatory response through the phosphoinositide 3-kinase (PI3K)/Akt or mitogen-activated protein kinase (MAPK) pathways in aged rats. Kangen-karyu or Salviae Miltiorrhizae Radix (20 mg/kg body weight/day) was administered orally to old groups of rats for 16 days, and their effects were compared with the vehicle-treated old and young rats. The administration of Kangen-karyu caused a slight decrease in the serum glucose level and a significant decrease in the serum insulin level in the old rats. The increased levels of serum renal functional parameter (urea-nitrogen) and oxidative parameter were significantly reduced by both Kangen-karyu and Salviae Miltiorrhizae Radix. The old rats exhibited a dysregulation of the protein expression related to insulin resistance, oxidative stress, and inflammation in the kidneys, but Kangen-karyu administration significantly reduced the expression of the inflammatory proteins through the PI3K/Akt pathway. On the other hand, the Salviae Miltiorrhizae Radix-treated old rats showed a decrease in the inflammatory cytokines through the MAPK pathway. These results provide important evidence that Kangen-karyu and Salviae Miltiorrhizae Radix have a pleiotropic effect on the PI3K/Akt and MAPK pathways, showing renoprotective effects against the development of inflammation in old rats. This study provides scientific evidence that Kangen-karyu and Salviae Miltiorrhizae Radix improve the inflammatory responses via the PI3K/Akt or MAPK pathways in the kidney of old rats.

scholarly journals Morin Attenuates Ovalbumin-Induced Airway Inflammation by Modulating Oxidative Stress-Responsive MAPK Signaling

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Yuan Ma ◽  
Ai Ge ◽  
Wen Zhu ◽  
Ya-Nan Liu ◽  
Ning-Fei Ji ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Airway Inflammation ◽  
Inflammatory Responses ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Intercellular Adhesion Molecule ◽  
Enzyme Linked Immunosorbent Assay ◽  
Chronic Asthma ◽  
Cell Counts

Asthma is one of the most common inflammatory diseases characterized by airway hyperresponsiveness, inflammation, and remodeling. Morin, an active ingredient obtained from Moraceae plants, has been demonstrated to have promising anti-inflammatory activities in a range of disorders. However, its impacts on pulmonary diseases, particularly on asthma, have not been clarified. This study was designed to investigate whether morin alleviates airway inflammation in chronic asthma with an emphasis on oxidative stress modulation.In vivo, ovalbumin- (OVA-) sensitized mice were administered with morin or dexamethasone before challenge. Bronchoalveolar lavage fluid (BALF) and lung tissues were obtained to perform cell counts, histological analysis, and enzyme-linked immunosorbent assay.In vitro, human bronchial epithelial cells (BECs) were challenged by tumor necrosis factor alpha (TNF-α). The supernatant was collected for the detection of the proinflammatory proteins, and the cells were collected for reactive oxygen species (ROS)/mitogen-activated protein kinase (MAPK) evaluations. Severe inflammatory responses and remodeling were observed in the airways of the OVA-sensitized mice. Treatment with morin dramatically attenuated the extensive trafficking of inflammatory cells into the BALF and inhibited their infiltration around the respiratory tracts and vessels. Morin administration also significantly suppressed goblet cell hyperplasia and collagen deposition/fibrosis and dose-dependently inhibited the OVA-induced increases in IgE, TNF-α, interleukin- (IL-) 4, IL-13, matrix metalloproteinase-9, and malondialdehyde. In human BECs challenged by TNF-α, the levels of proteins such as eotaxin-1, monocyte chemoattractant protein-1, IL-8 and intercellular adhesion molecule-1, were consistently significantly decreased by morin. Western blotting and the 2′,7′-dichlorofluorescein assay revealed that the increases in intracellular ROS and MAPK phosphorylation were abolished by morin, implying that ROS/MAPK signaling contributes to the relief of airway inflammation. Our findings indicate for the first time that morin alleviates airway inflammation in chronic asthma, which probably occurs via the oxidative stress-responsive MAPK pathway, highlighting a novel profile of morin as a potent agent for asthma management.

scholarly journals Glyoxal-Lysine Dimer, an Advanced Glycation End Product, Induces Oxidative Damage and Inflammatory Response by Interacting with RAGE

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1486
Author(s):  
Hee-Weon Lee ◽  
Min Ji Gu ◽  
Yoonsook Kim ◽  
Jee-Young Lee ◽  
Seungju Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Oxidative Damage ◽  
Inflammatory Responses ◽  
Mesangial Cells ◽  
Mitogen Activated Protein Kinase ◽  
Related Factor ◽  
Advanced Glycation ◽  
Advanced Glycation End Product ◽  
Mitogen Activated Protein

The glyoxal-lysine dimer (GOLD), which is a glyoxal (GO)-derived advanced glycation end product (AGE), is produced by the glycation reaction. In this study, we evaluated the effect of GOLD on the oxidative damage and inflammatory response in SV40 MES 13 mesangial cells. GOLD significantly increased the linkage with the V-type immunoglobulin domain of RAGE, a specific receptor of AGE. We found that GOLD treatment increased RAGE expression and reactive oxygen species (ROS) production in mesangial cells. GOLD remarkably regulated the protein and mRNA expression of nuclear factor erythroid 2-related factor 2 (NRF2) and glyoxalase 1 (GLO1). In addition, mitochondrial deterioration and inflammation occurred via GOLD-induced oxidative stress in mesangial cells. GOLD regulated the mitogen-activated protein kinase (MAPK) and the release of proinflammatory cytokines associated with the inflammatory mechanism of mesangial cells. Furthermore, oxidative stress and inflammatory responses triggered by GOLD were suppressed through RAGE inhibition using RAGE siRNA. These results demonstrate that the interaction of GOLD and RAGE plays an important role in the function of mesangial cells.

Age-Related Changes in Activation of Mitogen-Activated Protein Kinase Cascades by Oxidative Stress

1998 ◽  
Vol 3 (1) ◽  
pp. 23-27 ◽  
Author(s):  
Kathryn Z Guyton ◽  
Myriani Gorospe ◽  
Xiantao Wang ◽  
Yolanda D Mock ◽  
Gertrude C Kokkonen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Age Related ◽  
Mitogen Activated Protein ◽  
Age Related Changes

MKK3-p38 signaling promotes apoptosis and the early inflammatory response in the obstructed mouse kidney

2007 ◽  
Vol 293 (5) ◽  
pp. F1556-F1563 ◽  
Author(s):  
Frank Y. Ma ◽  
Greg H. Tesch ◽  
Richard A. Flavell ◽  
Roger J. Davis ◽  
David J. Nikolic-Paterson
Keyword(s):  
Inflammatory Response ◽  
P38 Mapk ◽  
Renal Injury ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Mrna Levels ◽  
Direct Role ◽  
Mitogen Activated Protein ◽  
Early Inflammatory Response ◽  
Induced Apoptosis

Activation of the p38 mitogen-activated protein kinase (MAPK) pathway induces inflammation, apoptosis, and fibrosis. However, little is known of the contribution of the upstream kinases, MMK3 and MKK6, to activation of the p38 kinase in the kidney and consequent renal injury. This study investigated the contribution of MKK3 to p38 MAPK activation and renal injury in the obstructed kidney. Groups of eight wild-type (WT) or Mkk3−/− mice underwent unilateral ureteric obstruction (UUO) and were killed 3 or 7 days later. Western blotting showed a marked increase in phospho-p38 (p-p38) MAPK in UUO WT kidney. The same trend of increased p-p38 MAPK was seen in the UUO Mkk3−/− kidney, although the actual level of p-p38 MAPK was significantly reduced compared with WT, and this could not be entirely compensated for by the increase in MKK6 expression in the Mkk3−/− kidney. Apoptosis of tubular and interstitial cells in WT UUO mice was reduced by 50% in Mkk3−/− UUO mice. Furthermore, cultured Mkk3−/− tubular epithelial cells showed resistance to H2O2-induced apoptosis, suggesting a direct role for MKK3-p38 signaling in tubular apoptosis. Upregulation of MCP-1 mRNA levels and macrophage infiltration seen on day 3 in WT UUO mice was significantly reduced in Mkk3−/− mice, but this difference was not evident by day 7. The development of renal fibrosis in Mkk3−/− UUO mice was not different from that seen in WT UUO mice. In conclusion, these studies identify discrete roles for MKK3-p38 signaling in renal cell apoptosis and the early inflammatory response in the obstructed kidney.

scholarly journals Functions for Cdc42p BEM Adaptors in Regulating a Differentiation-Type MAP Kinase Pathway

2019 ◽  
Author(s):  
Sukanya Basu ◽  
Beatriz González ◽  
Boyang Li ◽  
Garrett Kimble ◽  
Keith G. Kozminski ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cell Polarity ◽  
Rho Gtpase ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
List Type ◽  
Activation Kinetics ◽  
Closed Conformation ◽  
Mapk Pathways ◽  
Effector Pathways

ABSTRACTRho GTPases regulate cell polarity and signal transduction pathways to control morphogenetic responses in different settings. In yeast, the Rho GTPase Cdc42p regulates cell polarity, and through the p21-activated kinase Ste20p, Cdc42p also regulates mitogen-activated protein kinase (MAPK) pathways (mating, filamentous growth or fMAPK, and HOG). Although much is known about how Cdc42p regulates cell polarity and the mating pathway, how Cdc42p regulates the fMAPK pathway is not clear. To address this question, Cdc42p-dependent MAPK pathways were compared in the filamentous (∑1278b) strain background. Each MAPK pathway showed a unique activation profile, with the fMAPK pathway exhibiting slow activation kinetics compared to the mating and HOG pathways. A previously characterized version of Cdc42p, Cdc42pE100A, that is specifically defective for fMAPK pathway signaling, was defective for interaction with Bem4p, the pathway-specific adaptor for the fMAPK pathway. Corresponding residues in Bem4p were identified that were required for interaction with Cdc42p and fMAPK pathway signaling. The polarity adaptor Bem1p also regulated the fMAPK pathway. In the fMAPK pathway, Bem1p recruited Ste20p to the plasma membrane, cycled between an open and closed conformation, and interacted with the GEF for Cdc42, Cdc24p. Bem1p also regulated effector pathways in different ways, behaving as a multi-functional adaptor in some pathways and an inert scaffold in others. Genetic suppression tests showed that Bem4p and Bem1p regulate the fMAPK pathway in an ordered sequence. Collectively, the study demonstrates unique and sequential functions for Rho GTPase adaptors in regulating MAPK pathways.HIGHLIGHTSComparing Cdc42p-dependent MAPK pathways showed that the fMAPK pathway had slow activation kinetics compared to the mating and HOG pathways.A collection of cdc42 alleles was tested for MAPK pathway functions. § Cdc42pE100A, previously characterized as being specifically defective for fMAPK signaling, showed reduced interaction with the fMAPK pathway adaptor Bem4p.§ Corresponding residues in Bem4p were identified that were required for interaction with Cdc42p and fMAPK signaling.The polarity adaptor Bem1p regulated the fMAPK pathway. § Bem1p regulated the fMAPK pathway by recruiting Ste20p to the plasma membrane, cycling between an open and closed conformation, and interacting with the Cdc42p GEF, Cdc24p.Different domains of Bem1p had different roles in regulating effector pathways. § Bem1p may function as a multi-functional adaptor in some pathways and an inert scaffold in others.Bem4p and Bem1p regulated the fMAPK pathway in an ordered sequence. § The data support a model where Bem4p recruits Cdc24p to GDP-Cdc42p, and Bem1p directs GTP-Cdc42p to Ste20p at the plasma membrane.§ The bud-site GTPase Rsr1p regulates Cdc24p in the fMAPK pathway but does not initiate signaling.

scholarly journals Hydrogen Sulfide Gas Exposure Induces Necroptosis and Promotes Inflammation through the MAPK/NF-κB Pathway in Broiler Spleen

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Qianru Chi ◽  
Dongxu Wang ◽  
Xueyuan Hu ◽  
Shiping Li ◽  
Shu Li
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Sulfide ◽  
Energy Metabolism ◽  
Inflammatory Response ◽  
Human Health ◽  
Mapk Pathway ◽  
Classical Pathway ◽  
Inos Activity ◽  
Mda Content ◽  
Sulfur Containing

Hydrogen sulfide (H2S) is one of the main pollutants in the atmosphere, which is a serious threat to human health. The decomposition of sulfur-containing organics in chicken houses could produce a large amount of H2S, thereby damaging poultry health. In this study, one-day-old broilers were selected and exposed to 4 or 20 ppm of H2S gas (0-3 weeks: 4±0.5 ppm, 4-6 weeks: 20±0.5 ppm). The spleen samples were collected immediately after the chickens were euthanized at 2, 4, and 6 weeks. The histopathological and ultrastructural observations showed obvious necrosis characteristics of H2S-exposed spleens. H2S exposure suppressed GSH, CAT, T-AOC, and SOD activities; increased NO, H2O2, and MDA content and iNOS activity; and induced oxidative stress. ATPase activities and the expressions of energy metabolism-related genes were significantly decreased. Also, the expressions of related necroptosis (RIPK1, RIPK3, MLKL, TAK1, TAB2, and TAB3) were significantly increased, and the MAPK pathway was activated. Besides, H2S exposure activated the NF-κB classical pathway and induced TNF-α and IL-1β release. Taken together, we conclude that H2S exposure induces oxidative stress and energy metabolism dysfunction; evokes necroptosis; activates the MAPK pathway, eventually triggering the NF-κB pathway; and promotes inflammatory response in chicken spleens.

Role of oxidative stress in defective renal dopamine D1 receptor-G protein coupling and function in old Fischer 344 rats

2006 ◽  
Vol 291 (5) ◽  
pp. F945-F951 ◽  
Author(s):  
Riham Zein Fardoun ◽  
Mohammad Asghar ◽  
Mustafa Lokhandwala
Keyword(s):  
Oxidative Stress ◽  
G Protein ◽  
D1 Receptor ◽  
Serine Phosphorylation ◽  
D1 Receptors ◽  
Adult Rats ◽  
G Protein Coupling ◽  
Protein Coupling ◽  
Age Related ◽  
Old Rats

Aging is associated with an increase in oxidative stress. Previously, we have reported that dopamine failed to inhibit proximal tubular Na-K-ATPase and to promote sodium excretion in old rats (Beheray S, Kansra V, Hussain T, and Lokhandwala MF. Kidney Int 58: 712–720, 2000). This was due to uncoupling of dopamine D1 receptors from G proteins resulting from hyperphosphorylation of D1 receptors. The present study was designed to test the role of oxidative stress in the age-related decline in renal dopamine D1 receptor function. We observed that old animals had increased malondialdehyde (MDA) levels, a biomarker of oxidative stress, and decreased D1 receptor number and protein in the proximal tubules (PT) compared with adult rats. In old rats, there was increased G protein-coupled receptor kinase-2 (GRK-2) abundance, increased basal serine phosphorylation of D1 receptors, and defective D1 receptor-G protein coupling in PT membranes. Interestingly, supplementation with an antioxidant, tempol (1 mmol/l in drinking water for 15 days), lowered MDA levels and normalized D1 receptor number and protein in old rats to the level seen in adult rats. Furthermore, tempol decreased GRK-2 abundance and D1 receptor serine phosphorylation and restored D1 receptor-G protein coupling in PT of old rats. The functional consequence of these changes was the restoration of the natriuretic response to D1 receptor activation in tempol-supplemented old rats. Therefore, in old rats, tempol reduces oxidative stress and prevents GRK-2 membranous abundance and hyperphosphorylation of D1 receptors, resulting in restoration of D1 receptor-G protein coupling and the natriuretic response to SKF-38393. Thus tempol, by lowering oxidative stress, normalizes the age-related decline in dopamine receptor function.

scholarly journals Tolerogenic dendritic cells induced by atorvastatin via inhibition of the TLR-4/NF-κB pathway improve cardiac remodeling after myocardial infarction

2020 ◽  
Author(s):  
Jianbing Zhu ◽  
Hang Chen ◽  
Yuanji Ma ◽  
Haibo Liu ◽  
Zhaoyang Chen
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Dendritic Cells ◽  
Inflammatory Response ◽  
Infarct Size ◽  
Inflammatory Reaction ◽  
Ventricular Remodeling ◽  
Inflammatory Responses ◽  
Systolic Function ◽  
Left Ventricular

Abstract BackgroundNecrosis of ischemic cardiomyocytes after myocardial infarction (MI) activates an intense inflammatory reaction. Dendritic cells (DCs) play a crucial role in the repair process after MI. Tolerogenic DCs (tDCs) can inhibit inflammatory responses. Methods and resultsWe investigated the role of atorvastatin and supernatants of necrotic cardiomyocytes (SNC) on DCs. We found that SNC induced DCs maturation, activated TLR-4/NF-κB pathway, promoted inflammatory cytokines secretion and oxidative stress. Co-treatment with SNC and atorvastatin suppressed DC maturation and inflammatory response, which meant that atorvastatin induced DCs tolerate to SNC. Then, we investigated the effect of mDCs induced by SNC and tDCs induced by atorvastatin on ventricular remodeling after MI. tDCs treatment significantly improved the left ventricular systolic function, reduced the infiltration of MPO+ neutrophil, Mac3+ macrophages and CD3+ T cells, inhibited myocardial apoptosis and fibrosis, and decreased infarct size. Compared with PBS, treatment with mDCs did not showed beneficial effect on ventricular remodeling and inflammatory reaction after MI in mice.ConclusionAtorvastatin inactivated the TLR-4/NF-κB pathway, repressed the oxidative stress, inflammatory response, and immune maturity induced by SNC. Treatment with tDCs, induced by co-treated with atorvastatin, preserved left ventricular function, limited infarct size, suppressed the infiltration of inflammatory cells, and attenuated the severity of fibrosis, and reduced the number of apoptotic cardiomyocytes.

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.

Sign in / Sign up

Export Citation Format

Share Document