Oxidative-stress-induced epigenetic changes in chronic diabetic complications

2013 ◽  
Vol 91 (3) ◽  
pp. 213-220 ◽  
Author(s):  
Biao Feng ◽  
Michael Anthony Ruiz ◽  
Subrata Chakrabarti
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Protein Kinase ◽  
Diabetic Complications ◽  
Histone Deacetylases ◽  
Excision Repair ◽  
Mitogen Activated Protein Kinase ◽  
Signal Pathways ◽  
Epigenetic Changes ◽  
Class Iii

Oxidative stress plays an important role in the development and progression of chronic diabetic complications. Diabetes causes mitochondrial superoxide overproduction in the endothelial cells of both large and small vessels. This increased superoxide production causes the activation of several signal pathways involved in the pathogenesis of chronic complications. In particular, endothelial cells are major targets of glucose-induced oxidative damage in the target organs. Oxidative stress activates cellular signaling pathways and transcription factors in endothelial cells including protein kinase C (PKC), c-Jun-N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), forkhead box O (FOXO), and nuclear factor kappa-B (NF-κB). Oxidative stress also causes DNA damage and activates DNA nucleotide excision repair enzymes including the excision repair cross complimenting 1(ERCC1), ERCC4, and poly(ADP-ribose) polymerase (PARP). Augmented production of histone acetyltransferase p300, and alterations of histone deacetylases, including class III deacetylases sirtuins, are also involved in this process. Recent research has found that small noncoding RNAs, like microRNA, are a new kind of regulator associated with chronic diabetic complications. There are extensive and complicated interactions and among these molecules. The purpose of this review is to demonstrate the role of oxidative stress in the development of diabetic complications in relation to epigenetic changes such as acetylation and microRNA alterations.

Curcumin Down-Regulates Cytokine-Mediated Tissue Factor and Plasminogen Activator Type 1 Expression In Human Endothelial Cells

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3333-3333
Author(s):  
Eriko Morishita ◽  
Keiko Maruyama ◽  
Hidesaku Asakura ◽  
Shigeki Ohtake ◽  
Akihiro Yachie ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Tissue Factor ◽  
Plasminogen Activator ◽  
Conflicts Of Interest ◽  
Mitogen Activated Protein Kinase ◽  
Signal Pathways ◽  
Tnf Α ◽  
Pai 1

Abstract Abstract 3333 Curcumin (diferuloyl methane), an active component of the spice turmeric, has been shown to exhibit anti-inflammatory and antioxidant activities in addition to an anticartinogenic activity in vitro and in vivo. Recent studies reported that curcumin acts as a non-stressful and non-cytotoxic inducer of the cytoprotective heme oxigenase-1 (HO-1). HO-1 is an inducible enzyme which degrades oxidative heme into biliverdin, free iron, and carbon monoxide. The first human case of HO-1 deficiency was described from Japan by Yachie, et al (J Clin Invest 1999; 103:129). This HO-1 deficient child exhibited severe persistent endothelial damage and extremely hyper-coagulable state. These findings prompted us to study roles of HO-1 in the regulation of coagulability. Epstein-Barr virus-transformed lymphoblastoid cell line (LCL) derived from the HO-1 deficient patient was not able to produce HO-1 production at all. In comparison to control LCLs, the HO-1 deficient LCLs expressed markedly higher levels of tissue factor (TF) mRNA and protein (2-fold, p<0.05) as well as of plasminogen activator inhibitor type 1 (PAI-1) (2-fold, p<0.05), upon exposure to oxidative stress such as hemin, suggested important roles of HO-1 or HO-1 products in the regulating of coagulation and fibrinolytic system. We then hypothesized that endothelial HO-1 induced by curcumin may ameliorate hyper-coagulable state associated with inflammation or oxidative stress. The exposure of human umbilical vein endothelial cells (HUVECs) to curcumin (15 mM) for 6 hr resulted in a significant increase in the level of both HO-1 mRNA (15-fold) and protein. The treatment of HUVECs with 15 mM curcumin for 3hr before stimulation with tumor necrosis factor-α (TNF-α, 10 ng/ml) for additional 5hr markedly inhibited TNF-a-induced expression of TF (approximately 90 % suppression) and PAI-1 (approximately 70 % suppression) (Figure1). The inhibitory effect of curcumin on the TF expression was partially abrogated by tin protoporphyrin IX (SnPP) (20 mM), an inhibitor of heme oxigenase activity, indicating that the curcumin-induced suppression of TF is partly mediated by HO-1 (Figure 1). Moreover, curcumin inhibited TNF-a-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase 1and 2 (ERK1/2), and c-Jun N-terminal kinase (JNK), indicating the inhibition of these signal pathways may also be responsible for the suppression of TF/PAI-1 expressions in HUVECs by curcumin. In conclusion, these results indicate that curcumin exerts anti-thrombotic effects directly and indirectly through the induction of HO-1. Curcumin may serve as a novel anti-thrombotic agent for the treatment of hyper-coagulable state or thrombus formation associated with inflammation. Figure 1. Effects of curcumin on TNF-α-induced TF and PAI-1 protein (A) and mRNA (B) expression in HUVECs. The columns represent the mean ± SD (n=3) percentages of the control culture. *p<0.05 versus TNF-α alone. Disclosures: No relevant conflicts of interest to declare.

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

scholarly journals Sanghuangporus sanghuang Mycelium Prevents Paracetamol-Induced Hepatotoxicity through Regulating the MAPK/NF-κB, Keap1/Nrf2/HO-1, TLR4/PI3K/Akt and CaMKKβ/LKB1/AMPK Pathways and Suppressing Oxidative Stress and Inflammation

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 897
Author(s):  
Wen-Ping Jiang ◽  
Jeng-Shyan Deng ◽  
Shyh-Shyun Huang ◽  
Sheng-Hua Wu ◽  
Chin-Chu Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Mitogen Activated Protein Kinase ◽  
Heme Oxygenase 1 ◽  
Molecular Evidence ◽  
Related Factor ◽  
Serum Aminotransferase ◽  
Compound C

Liver damage induced by paracetamol overdose is the main cause of acute liver failure worldwide. In order to study the hepatoprotective effect of Sanghuangporus sanghuang mycelium (SS) on paracetamol-induced liver injury, SS was administered orally every day for 6 days in mice before paracetamol treatment. SS decreased serum aminotransferase activities and the lipid profiles, protecting against paracetamol hepatotoxicity in mice. Furthermore, SS inhibited the lipid peroxidation marker malondialdehyde (MDA), hepatic cytochrome P450 2E1 (CYP2E1), and the histopathological changes in the liver and decreased inflammatory activity by inhibiting the production of proinflammatory cytokines in paracetamol-induced acute liver failure. Moreover, SS improved the levels of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase in the liver. Significantly, SS diminished mitogen-activated protein kinase (MAPK), Toll-like receptor 4 (TLR4), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and the nuclear factor-kappa B (NF-κB) axis, as well as upregulated the Kelch-like ECH-associated protein 1 (Keap1)/erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, in paracetamol-induced mice. SS mainly inhibited the phosphorylation of the liver kinase B1 (LKB1), Ca2+/calmodulin-dependent kinase kinase β (CaMKKβ), and AMP-activated protein kinase (AMPK) protein expression. Furthermore, the protective effects of SS on paracetamol-induced hepatotoxicity were abolished by compound C, an AMPK inhibitor. In summary, we provide novel molecular evidence that SS protects liver cells from paracetamol-induced hepatotoxicity by inhibiting oxidative stress and inflammation.

Sign in / Sign up

Export Citation Format

Share Document