Cytoglobin Promotes Cardiac Progenitor Cell Survival against Oxidative Stress via the Upregulation of the NFκB/iNOS Signal Pathway and Nitric Oxide Production

Zhang, Shuning; Li, Xiuchun; Jourd’heuil, Frances; Qu, Shunlin; Devejian, Neil; Bennett, Edward V.; Jourd’heuil, David; Cai, Chuanxi

doi:10.1038/s41598-017-11342-6

Cited by 34 publications

(35 citation statements)

References 59 publications

(77 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although recent studies have investigated antioxidant systems in hypertension and its role to oppose oxidative stress [ 31 , 32 ], very few is known about their response to exercise training in the heart of hypertensive individuals. Therefore, we also analyzed in the LV of both strains the effects of aerobic training on several antioxidant enzymes.…”

Section: Resultsmentioning

confidence: 99%

Temporal changes in cardiac oxidative stress, inflammation and remodeling induced by exercise in hypertension: Role for local angiotensin II reduction

et al. 2017

View full text Add to dashboard Cite

Exercise training reduces renin-angiotensin system (RAS) activation, decreases plasma and tissue oxidative stress and inflammation in hypertension. However, the temporal nature of these phenomena in response to exercise is unknown. We sought to determine in spontaneously hypertensive rats (SHR) and age-matched WKY controls the weekly effects of training on blood pressure (BP), plasma and left ventricle (LV) Ang II and Ang-(1–7) content (HPLC), LV oxidative stress (DHE staining), gene and protein expression (qPCR and WB) of pro-inflammatory cytokines, antioxidant enzymes and their consequence on hypertension-induced cardiac remodeling. SHR and WKY were submitted to aerobic training (T) or maintained sedentary (S) for 8 weeks; measurements were made at weeks 0, 1, 2, 4 and 8. Hypertension-induced cardiac hypertrophy was accompanied by acute plasma Ang II increase with amplified responses during the late phase of LV hypertrophy. Similar pattern was observed for oxidative stress markers, TNF alpha and interleukin-1β, associated with cardiomyocytes’ diameter enlargement and collagen deposition. SHR-T exhibited prompt and marked decrease in LV Ang II content (T1 vs T4 in WKY-T), normalized oxidative stress (T2), augmented antioxidant defense (T4) and reduced both collagen deposition and inflammatory profile (T8), without changing cardiomyocytes’ diameter and LV hypertrophy. These changes were accompanied by decreased plasma Ang II content (T2-T4) and reduced BP (T8). SHR-T and WKY-T showed parallel increases in LV and plasma Ang-(1–7) content. Our data indicate that early training-induced downregulation of LV ACE-AngII-AT1 receptor axis is a crucial mechanism to reduce oxidative/pro-inflammatory profile and improve antioxidant defense in SHR-T, showing in addition this effect precedes plasma RAS deactivation.

show abstract

Section: Resultsmentioning

confidence: 99%

Temporal changes in cardiac oxidative stress, inflammation and remodeling induced by exercise in hypertension: Role for local angiotensin II reduction

et al. 2017

View full text Add to dashboard Cite

show abstract

“…However, in the case of iNOS, activation can result in positive feedforward accumulation of iNOS, resulting in a pathogenic effect. ( 33 ) We measured Nos1, Nos2 (iNOS), and Nos3 levels in the livers of mice from the eight groups and found that while Nos1 and Nos3 were unchanged or down‐regulated in knockout mice (Supporting Fig. ), iNOS expression was induced in the male PRMT1‐knockout mice fed alcohol, the group with the highest median tumor number (Fig.…”

Section: Resultsmentioning

confidence: 95%

Hepatocellular Protein Arginine Methyltransferase 1 Suppresses Alcohol‐Induced Hepatocellular Carcinoma Formation by Inhibition of Inducible Nitric Oxide Synthase

et al. 2020

View full text Add to dashboard Cite

Alcohol is a well-established risk factor for hepatocellular carcinoma (HCC), but the mechanisms by which alcohol promotes liver cancer are not well understood. Studies suggest that ethanol may enhance tumor progression by increasing hepatocyte proliferation and through alcohol-induced liver inflammation. Protein arginine methyltransferase 1 (PRMT1) is the main enzyme responsible for cellular arginine methylation. Asymmetric dimethyl arginine, produced by PRMT1, is a potent inhibitor of nitric oxide synthases. PRMT1 is implicated in the development of several types of tumors and cardiovascular disease. Our previous work has shown that PRMT1 in the liver regulates hepatocyte proliferation and oxidative stress and protects from alcohol-induced liver injury. However, its role in HCC development remains controversial. In this study, we found that hepatocyte-specific PRMT1-knockout mice develop an increased number of tumors in an N-nitrosodiethylamine (DEN) alcohol model of liver tumorigenesis in mice. This effect was specific to the alcohol-related component because wild-type and knockout mice developed similar tumor numbers in the DEN model without the addition of alcohol. We found that in the presence of alcohol, the increase in tumor number was associated with increased proliferation in liver and tumor, increased WNT/β-catenin signaling, and increased inflammation. We hypothesized that increased inflammation was due to increased oxidative and nitrosative stress in knockout mice. By blocking excess nitric oxide production using an inducible nitric oxide synthase inhibitor, we reduced hepatocyte death and inflammation in the liver and prevented the increase in WNT/β-catenin signaling, proliferation, and tumor number in livers of knockout mice. Conclusion: PRMT1 is an important protection factor from alcohol-induced liver injury, inflammation, and HCC development. (Hepatology Communications 2020;4:790-808). SEE EDITORIAL ON PAGE 787H epatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide. (1,2) Unlike other cancers with known risk factors, molecular mechanisms of HCC development are not completely understood. Most patients with HCC have a history of chronic liver disease and cirrhosis, (3) but cirrhosis associated with hepatitis B and C and chronic alcohol drinking account for most cases. (4) About 40% of individuals who chronically consume alcohol develop fatty liver, which can advance to alcoholic hepatitis and/or cirrhosis. Although there have been conflicting findings, currently it is accepted that

show abstract

“…Human cardiac progenitor cells (hCPCs) were isolated from the right atrial appendage and sorted for expression of c-kit cell surface marker, as described previously (Zhang et al, 2017). Cells were used at passage 7-10 for these studies.…”

Section: Culture Of Cardiac Progenitor Cellsmentioning

confidence: 99%

Human Cardiac Progenitor Cells Enhance Exosome Release and Promote Angiogenesis Under Physoxia

Dougherty

Patel

Kumar

et al. 2020

Front. Cell Dev. Biol.

Self Cite

View full text Add to dashboard Cite

Studies on cardiac progenitor cells (CPCs) and their derived exosomes therapeutic potential have demonstrated only modest improvements in cardiac function. Therefore, there is an unmet need to improve the therapeutic efficacy of CPCs and their exosomes to attain clinically relevant improvement in cardiac function. The hypothesis of this project is to assess the therapeutic potential of exosomes derived from human CPCs (hCPCs) cultured under normoxia (21% O 2), physoxia (5% O 2) and hypoxia (1% O 2) conditions. hCPCs were characterized by immunostaining of CPC-specific markers (NKX-2.5, GATA-4, and c-kit). Cell proliferation and cell death assay was not altered under physoxia. A gene expression qPCR array (84 genes) was performed to assess the modulation of hypoxic genes under three different oxygen conditions as mentioned above. Our results demonstrated that very few hypoxia-related genes were modulated under physoxia (5 genes upregulated, 4 genes down regulated). However, several genes were modulated under hypoxia (23 genes upregulated, 9 genes downregulated). Furthermore, nanoparticle tracking analysis of the exosomes isolated from hCPCs under physoxia had a 1.6-fold increase in exosome yield when compared to normoxia and hypoxia conditions. Furthermore, tube formation assay for angiogenesis indicated that exosomes derived from hCPCs cultured under physoxia significantly increased tube formation as compared to no-exosome control, 21% O 2 , and 1% O 2 groups. Overall, our study demonstrated the therapeutic potential of physoxic oxygen microenvironment cultured hCPCs and their derived exosomes for myocardial repair.

show abstract

Cytoglobin Promotes Cardiac Progenitor Cell Survival against Oxidative Stress via the Upregulation of the NFκB/iNOS Signal Pathway and Nitric Oxide Production

Cited by 34 publications

References 59 publications

Temporal changes in cardiac oxidative stress, inflammation and remodeling induced by exercise in hypertension: Role for local angiotensin II reduction

Temporal changes in cardiac oxidative stress, inflammation and remodeling induced by exercise in hypertension: Role for local angiotensin II reduction

Hepatocellular Protein Arginine Methyltransferase 1 Suppresses Alcohol‐Induced Hepatocellular Carcinoma Formation by Inhibition of Inducible Nitric Oxide Synthase

Human Cardiac Progenitor Cells Enhance Exosome Release and Promote Angiogenesis Under Physoxia

Contact Info

Product

Resources

About