Nano-Curcumin Protects Against Sodium Nitrite–Induced Lung Hypoxia Through Modulation of Mitogen-Activated Protein Kinases/c-Jun NH2-Terminal Kinase Signaling Pathway

Background and objective This study was designed to compare the efficacy of curcumin (CRN) with that of nano-curcumin (N-CRN) in the mitigation of various biochemical indices in hypoxic lung induced by sodium nitrite (SN) in rats. Methods Twenty-four adult male albino rats were divided into 4 groups. Group 1: control group received carboxy methyl cellulose; Group 2: hypoxic group injected with single dose of SN (60 mg/kg, s.c.); Group 3: SN-intoxicated rats pre-injected with CRN (100 mg/kg, i.p.); and Group 4: SN-intoxicated rats pre-injected with N-CRN (100 mg/kg, i.p.). Curcumin and N-CRN were administered intraperitoneally 2 hour prior to SN intoxication. Hemoglobin concentration, serum tumor necrosis factor-alpha (TNF-α), and caspase-3 were analyzed. Gene expression of hypoxia inducible factor-1 (HIF-1α), matrix metallo-proteinases (MMP)-2, and tissue inhibitors of metalloproteinases (TIMPs)-2, as well as the protein expression of mitogen-activated protein kinases (MAPKs) and c-Jun NH2-terminal kinase (JNK) were examined in lung tissues. Results Hemoglobin level was markedly reduced, and serum TNF-α and caspase-3 were significantly elevated post SN intoxication. The lung MMP-2 and HIF-1α mRNA were overexpressed in the hypoxic group; while TIMP-2 mRNA was downregulated. Sodium nitrite administration increased proteins’ expressions of MAPK and JNK. Pretreatment with CRN or N-CRN markedly mitigated those alterations. These results were supported by histopathological examinations of lung tissue. Conclusion Interestingly, N-CRN exhibited a pronounced protective effect via suppression of inflammatory and apoptotic biomarkers and modulation of MAPK/JNK signaling pathway.

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HIV-1-infected and/or immune-activated macrophages regulate astrocyte CXCL8 production through IL-1β and TNF-α: Involvement of mitogen-activated protein kinases and protein kinase R

Journal of Neuroimmunology ◽

10.1016/j.jneuroim.2008.06.015 ◽

2008 ◽

Vol 200 (1-2) ◽

pp. 100-110 ◽

Cited By ~ 37

Author(s):

Jialin C. Zheng ◽

Yunlong Huang ◽

Kang Tang ◽

Min Cui ◽

Doug Niemann ◽

...

Keyword(s):

Protein Kinase ◽

Protein Kinases ◽

Activated Macrophages ◽

Protein Kinase R ◽

Mitogen Activated Protein Kinases ◽

Tnf Α ◽

Mitogen Activated Protein ◽

Hiv 1

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Hydrogen sulfide‐induced apoptosis of human aorta smooth muscle cells via the activation of mitogen‐activated protein kinases and caspase‐3

The FASEB Journal ◽

10.1096/fj.04-2279fje ◽

2004 ◽

Vol 18 (14) ◽

pp. 1782-1784 ◽

Cited By ~ 209

Author(s):

Guangdong Yang ◽

Xianfeng Sun ◽

Rui Wang

Keyword(s):

Smooth Muscle ◽

Hydrogen Sulfide ◽

Smooth Muscle Cells ◽

Protein Kinases ◽

Caspase 3 ◽

Muscle Cells ◽

Human Aorta ◽

Mitogen Activated Protein Kinases ◽

Mitogen Activated Protein ◽

Induced Apoptosis

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Modulation of autocrine TNF-α-stimulated matrix metalloproteinase 9 (MMP-9) expression by mitogen-activated protein kinases in THP-1 monocytic cells

Biological Chemistry ◽

10.1515/bc.2006.010 ◽

2006 ◽

Vol 387 (1) ◽

Cited By ~ 35

Author(s):

Michael Heidinger ◽

Helmut Kolb ◽

Hans-Willi Krell ◽

Marianne Jochum ◽

Christian Ries

Keyword(s):

Matrix Metalloproteinase ◽

Protein Kinases ◽

Matrix Metalloproteinase 9 ◽

Monocytic Cells ◽

Mitogen Activated Protein Kinases ◽

Tnf Α ◽

Mitogen Activated Protein ◽

Metalloproteinase 9

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Selective inhibition of TNF-α-induced activation of mitogen-activated protein kinases and metastatic activities by gefitinib

British Journal of Cancer ◽

10.1038/sj.bjc.6602548 ◽

2005 ◽

Vol 92 (9) ◽

pp. 1690-1695 ◽

Cited By ~ 23

Author(s):

Y Ueno ◽

H Sakurai ◽

M Matsuo ◽

M K Choo ◽

K Koizumi ◽

...

Keyword(s):

Protein Kinases ◽

Selective Inhibition ◽

Mitogen Activated Protein Kinases ◽

Tnf Α ◽

Mitogen Activated Protein

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γ-mangostin attenuates amyloid-β42-induced neuroinflammation and oxidative stress in microglia-like BV2 cells via the mitogen-activated protein kinases signaling pathway

European Journal of Pharmacology ◽

10.1016/j.ejphar.2022.174744 ◽

2022 ◽

pp. 174744

Author(s):

Chaojun Kong ◽

Longfei Jia ◽

Jianping Jia

Keyword(s):

Oxidative Stress ◽

Signaling Pathway ◽

Protein Kinases ◽

Mitogen Activated Protein Kinases ◽

Bv2 Cells ◽

Mitogen Activated Protein ◽

And Oxidative Stress

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Two distinct roles of mitogen-activated protein kinases in platelets and a novel Rac1-MAPK–dependent integrin outside-in retractile signaling pathway

Blood ◽

10.1182/blood-2008-05-155978 ◽

2009 ◽

Vol 113 (4) ◽

pp. 893-901 ◽

Cited By ~ 121

Author(s):

Panagiotis Flevaris ◽

Zhenyu Li ◽

Guoying Zhang ◽

Yi Zheng ◽

Junling Liu ◽

...

Keyword(s):

Ligand Binding ◽

Signaling Pathway ◽

Protein Kinases ◽

Stimuli Responsive ◽

Clot Retraction ◽

Mapk Activation ◽

Mitogen Activated Protein Kinases ◽

Integrin Αiibβ3 ◽

Mitogen Activated Protein ◽

Mlc Phosphorylation

Abstract Mitogen-activated protein kinases (MAPK), p38, and extracellular stimuli-responsive kinase (ERK), are acutely but transiently activated in platelets by platelet agonists, and the agonist-induced platelet MAPK activation is inhibited by ligand binding to the integrin αIIbβ3. Here we show that, although the activation of MAPK, as indicated by MAPK phosphorylation, is initially inhibited after ligand binding to integrin αIIbβ3, integrin outside-insignaling results in a late but sustained activation of MAPKs in platelets. Furthermore, we show that the early agonist-induced MAPK activation and the late integrin-mediated MAPK activation play distinct roles in different stages of platelet activation. Agonist-induced MAPK activation primarily plays an important role in stimulating secretion of platelet granules, while integrin-mediated MAPK activation is important in facilitating clot retraction. The stimulatory role of MAPK in clot retraction is mediated by stimulating myosin light chain (MLC) phosphorylation. Importantly, integrin-dependent MAPK activation, MAPK-dependent MLC phosphorylation, and clot retraction are inhibited by a Rac1 inhibitor and in Rac1 knockout platelets, indicating that integrin-induced activation of MAPK and MLC and subsequent clot retraction is Rac1-dependent. Thus, our results reveal 2 different activation mechanisms of MAPKs that are involved in distinct aspects of platelet function and a novel Rac1-MAPK–dependent cell retractile signaling pathway.

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