scholarly journals Nucleotide-Binding Oligomerization Domain-Like Receptor 3 Deficiency Attenuated Isoproterenol-Induced Cardiac Fibrosis via Reactive Oxygen Species/High Mobility Group Box 1 Protein Axis

2020 ◽  
Vol 8 ◽  
Author(s):  
Chen Liu ◽  
Tongtong Hu ◽  
Zhulan Cai ◽  
Qingwen Xie ◽  
Yuan Yuan ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cardiac Fibrosis ◽  
High Mobility ◽  
Reactive Oxygen ◽  
Nucleotide Binding ◽  
High Mobility Group ◽  
Oxygen Species ◽  
Oligomerization Domain

scholarly journals High-mobility group box 1 links sensing of reactive oxygen species by huntingtin to its nuclear entry

2018 ◽  
Vol 294 (6) ◽  
pp. 1915-1923 ◽  
Author(s):  
Susie Son ◽  
Laura E. Bowie ◽  
Tamara Maiuri ◽  
Claudia L. K. Hung ◽  
Carly R. Desmond ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
High Mobility ◽  
Reactive Oxygen ◽  
High Mobility Group ◽  
Oxygen Species ◽  
Nuclear Entry

scholarly journals Absence of the NOD2 protein renders epithelia more susceptible to barrier dysfunction due to mitochondrial dysfunction

2017 ◽  
Vol 313 (1) ◽  
pp. G26-G38 ◽  
Author(s):  
Alpana Saxena ◽  
Fernando Lopes ◽  
Karen K. H. Poon ◽  
Derek M. McKay
Keyword(s):  
Reactive Oxygen Species ◽  
Barrier Function ◽  
Paneth Cell ◽  
Metabolic Stress ◽  
Reactive Oxygen ◽  
Nucleotide Binding ◽  
Intracellular Bacteria ◽  
Oxygen Species ◽  
E Coli ◽  
Oligomerization Domain

Irregular mitochondria structure and reduced ATP in some patients with IBD suggest that metabolic stress contributes to disease. Loss-of-function mutation in the nucleotide-binding oligomerization domain (NOD)-2 gene is a major susceptibility trait for IBD. Hence, we assessed if loss of NOD2 further impairs the epithelial barrier function instigated by disruption of mitochondrial ATP synthesis via the hydrogen ionophore dinitrophenol (DNP). NOD2 protein (virtually undetectable in epithelia under basal conditions) was increased in T84 (human colon cell line) cells treated with noninvasive Escherichia coli + DNP (16 h). Increased intracellular bacteria in wild-type (WT) and NOD2 knockdown (KD) cells and colonoids from NOD2−/− mice were mediated by reactive oxygen species (ROS) and the MAPK ERK1/2 pathways as determined by cotreatment with the antioxidant mitoTEMPO and the ERK inhibitor U0126: ROS was upstream of ERK1/2 activation. Despite increased E. coli in DNP-treated NOD2 KD compared with WT cells, there were no differences in the internalization of fluorescent inert beads or dead E. coli particles. This suggests that lack of killing in the NOD2 KD cells was responsible for the increased numbers of viable intracellular bacteria; a conclusion supported by evidence of reduced autophagy in NOD2 KD T84 epithelia. Thus, in a two-hit hypothesis, decreased barrier function due to dysfunctional mitochondrial is amplified by lack of NOD2 in transporting enterocytes: subsequently, greater numbers of bacteria entering the mucosa would be a significant inflammatory threat especially since individuals with NOD2 mutations have compromised macrophage and Paneth cell responses to bacteria. NEW & NOTEWORTHY Increased internalization of bacteria by epithelia with dysfunctional mitochondria (reduced ATP) is potentiated if the cells lack nucleotide-binding oligomerization domain 2 (NOD2), mutations in which are inflammatory bowel disease-susceptibility traits. Uptake of bacteria was dependent on reactive oxygen species and MAP-kinase activity, and the increased viable intracellular bacteria in NOD2−/− cells likely reflect a reduced ability to recognize and kill bacteria. Thus a significant barrier defect occurs with NOD2 deficiency in conjunction with metabolic stress that could contribute to inflammation.

scholarly journals Blue Light Induces Impaired Autophagy through Nucleotide-Binding Oligomerization Domain 2 Activation on the Mouse Ocular Surface

2021 ◽  
Vol 22 (4) ◽  
pp. 2015
Author(s):  
Ying Li ◽  
Rujun Jin ◽  
Lan Li ◽  
Ji Suk Choi ◽  
Jonghwa Kim ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Blue Light ◽  
Ocular Surface ◽  
Light Exposure ◽  
Reactive Oxygen ◽  
Nucleotide Binding ◽  
Oxygen Species ◽  
Knock Out ◽  
Corneal Epithelial ◽  
Oligomerization Domain

In this study, we investigated the effects of blue light exposure on nucleotide-binding oligomerization domain 2 (NOD2) expression on the mouse ocular surface and evaluated the role of NOD2 activation in light-induced cell death. Mice were divided into wild-type (WT), NOD2-knock out (KO), WT + blue light (WT + BL), and NOD2-KO + blue light (NOD2-KO + BL) groups, and the mice in the WT+BL and NOD2-KO + BL groups were exposed to blue light for 10 days. After 10 days of blue light exposure, increased reactive oxygen species and malondialdehyde were observed in the WT + BL and NOD2-KO + BL groups, and the WT + BL group showed a higher expression of NOD2 and autophagy related 16 like 1. Although both WT+BL and NOD2-KO + BL groups showed an increase in the expression of light chain 3-II, NOD2-KO + BL mice had a significantly lower p62 expression than WT + BL mice. In addition, NOD2-KO+BL mice had significantly lower corneal epithelial damage and apoptosis than WT + BL mice. In conclusion, blue light exposure can induce impaired autophagy by activation of NOD2 on the ocular surface. In addition, the reactive oxygen species (ROS)–NOD2–autophagy related 16 like 1 (ATG16L) signaling pathway may be involved in the blue-light-induced autophagy responses, resulting in corneal epithelial apoptosis.

scholarly journals Danshenol A Alleviates Hypertension-Induced Cardiac Remodeling by Ameliorating Mitochondrial Dysfunction and Suppressing Reactive Oxygen Species Production

2019 ◽  
Vol 2019 ◽  
pp. 1-18
Author(s):  
Kai Chen ◽  
Yiqing Guan ◽  
Yunci Ma ◽  
Dongling Quan ◽  
Jingru Zhang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Mitochondrial Dysfunction ◽  
Cardiac Remodeling ◽  
Cardiac Fibrosis ◽  
Spontaneously Hypertensive Rat ◽  
Cardiac Injury ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Spontaneously Hypertensive ◽  
Underlying Mechanisms

Current therapeutic approaches have a limited effect on cardiac remodeling, which is characteristic of cardiac fibrosis and myocardial hypertrophy. In this study, we examined whether Danshenol A (DA), an active ingredient extracted from the traditional Chinese medicine Radix Salviae, can attenuate cardiac remodeling and clarified the underlying mechanisms. Using the spontaneously hypertensive rat (SHR) as a cardiac remodeling model, DA ameliorated blood pressure, cardiac injury, and myocardial collagen volume and improved cardiac function. Bioinformatics analysis revealed that DA might attenuate cardiac remodeling through modulating mitochondrial dysfunction and reactive oxygen species. DA repaired the structure/function of the mitochondria, alleviated oxidative stress in the myocardium, and restored apoptosis of cardiomyocytes induced by angiotensin II. Besides, DA inhibited mitochondrial redox signaling pathways in both the myocardium and cardiomyocytes. Thus, our study suggested that DA attenuates cardiac remodeling induced by hypertension through modulating mitochondrial dysfunction and reactive oxygen species.

scholarly journals Endostatin attenuates heart failure via inhibiting reactive oxygen species in myocardial infarction rats

2020 ◽  
Author(s):  
Xuguang Xu ◽  
Tingbo Jiang ◽  
Yong Li ◽  
Liusha Kong
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Reactive Oxygen Species ◽  
Cardiac Function ◽  
Cardiac Fibrosis ◽  
Smooth Muscle Actin ◽  
Reactive Oxygen ◽  
Tissue Growth ◽  
Oxygen Species ◽  
Collagen Iii

The purpose of the present study was to evaluate whether endostatin overexpression could improve cardiac function, hemodynamics, and fibrosis in heart failure (HF) via inhibiting reactive oxygen species (ROS). The HF models were established by inducing ischemia myocardial infarction (MI) through ligation of the left anterior descending (LAD) artery in Sprague-Dawley (SD) rats. Endostatin level in serum was increased in MI rats. The decreases of cardiac function and hemodynamics in MI rats were enhanced by endostatin overexpression. Endostatin overexpression inhibited the increases of collagen I, collagen III, α-smooth muscle actin (SMA), connective tissue growth factor (CTGF), matrix metalloproteinase (MMP)-2 and MMP9 in the heart of MI rats. MI-induced cardiac hypertrophy was reduced by endostatin overexpression. The increased levels of malondialdehyde (MDA), superoxide anions, the promoted NAD(P)H oxidase (Nox) activity, and the reduced superoxide dismutase (SOD) activity in MI rats were reversed by endostatin overexpression. Nox4 overexpression inhibited the cardiac protective effects of endostatin. These results demonstrated that endostatin improved cardiac dysfunction and hemodynamics, and attenuated cardiac fibrosis and hypertrophy via inhibiting oxidative stress in MI-induced HF rats.

Sign in / Sign up

Export Citation Format

Share Document