scholarly journals Carbon Monoxide Releasing Molecule-2-Upregulated ROS-Dependent Heme Oxygenase-1 Axis Suppresses Lipopolysaccharide-Induced Airway Inflammation

2019 ◽  
Vol 20 (13) ◽  
pp. 3157 ◽  
Author(s):  
Chih-Chung Lin ◽  
Li-Der Hsiao ◽  
Rou-Ling Cho ◽  
Chuen-Mao Yang
Keyword(s):  
Carbon Monoxide ◽  
Western Blot ◽  
Airway Inflammation ◽  
Real Time ◽  
Heme Oxygenase ◽  
Real Time Pcr ◽  
Molecular Mechanisms ◽  
Intercellular Adhesion Molecule ◽  
Ros Generation ◽  
Heme Oxygenase 1

The up-regulation of heme oxygenase-1 (HO-1) is mediated through nicotinamaide adenine dinucleotide phosphate (NADPH) oxidases (Nox) and reactive oxygen species (ROS) generation, which could provide cytoprotection against inflammation. However, the molecular mechanisms of carbon monoxide-releasing molecule (CORM)-2-induced HO-1 expression in human tracheal smooth muscle cells (HTSMCs) remain unknown. Here, we found that pretreatment with CORM-2 attenuated the lipopolysaccharide (LPS)-induced intercellular adhesion molecule (ICAM-1) expression and leukocyte count through the up-regulation of HO-1 in mice, which was revealed by immunohistochemistrical staining, Western blot, real-time PCR, and cell count. The inhibitory effects of HO-1 by CORM-2 were reversed by transfection with HO-1 siRNA. Next, Western blot, real-time PCR, and promoter activity assay were performed to examine the HO-1 induction in HTSMCs. We found that CORM-2 induced HO-1 expression via the activation of protein kinase C (PKC)α and proline-rich tyrosine kinase (Pyk2), which was mediated through Nox-derived ROS generation using pharmacological inhibitors or small interfering ribonucleic acids (siRNAs). CORM-2-induced HO-1 expression was mediated through Nox-(1, 2, 4) or p47phox, which was confirmed by transfection with their own siRNAs. The Nox-derived ROS signals promoted the activities of extracellular signal-regulated kinase 1/2 (ERK1/2). Subsequently, c-Fos and c-Jun—activator protein-1 (AP-1) subunits—were up-regulated by activated ERK1/2, which turned on transcription of the HO-1 gene by regulating the HO-1 promoter. These results suggested that in HTSMCs, CORM-2 activates PKCα/Pyk2-dependent Nox/ROS/ERK1/2/AP-1, leading to HO-1 up-regulation, which suppresses the lipopolysaccharide (LPS)-induced airway inflammation.

scholarly journals Renal protection in chronic kidney disease: hypoxia-inducible factor activation vs. angiotensin II blockade

2010 ◽  
Vol 299 (6) ◽  
pp. F1365-F1373 ◽  
Author(s):  
Aihua Deng ◽  
Mary Ann K. Arndt ◽  
Joseph Satriano ◽  
Prabhleen Singh ◽  
Timo Rieg ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Oxygen Consumption ◽  
Angiotensin Ii ◽  
Kidney Disease ◽  
Real Time ◽  
Heme Oxygenase ◽  
Real Time Pcr ◽  
Hypoxia Inducible Factor ◽  
Heme Oxygenase 1 ◽  
Ang Ii

The 5/6thnephrectomy or ablation/infarction (A/I) preparation has been used as a classic model of chronic kidney disease (CKD). We observed increased kidney oxygen consumption (QO2) and altered renal hemodynamics in the A/I kidney that were normalized after combined angiotensin II (ANG II) blockade. Studies suggest hypoxia inducible factor as a protective influence in A/I. We induced hypoxia-inducible factor (HIF) and HIF target proteins by two different methods, cobalt chloride (CoCl2) and dimethyloxalyglycine (DMOG), for the first week after creation of A/I and compared the metabolic and renal hemodynamic outcomes to combined ANG II blockade. We also examined the HIF target proteins expressed by using Western blots and real-time PCR. Treatment with DMOG, CoCl2, and ANG II blockade normalized kidney oxygen consumption factored by Na reabsorption and increased both renal blood flow and glomerular filtration rate. At 1 wk, CoCl2and DMOG increased kidney expression of HIF by Western blot. In the untreated A/I kidney, VEGF, heme oxygenase-1, and GLUT1 were all modestly increased. Both ANG II blockade and CoCl2therapy increased VEGF and GLUT1 but the cobalt markedly so. ANG II blockade decreased heme oxygenase-1 expression while CoCl2increased it. By real-time PCR, erythropoietin and GLUT1 were only increased by CoCl2therapy. Cell proliferation was modestly increased by ANG II blockade but markedly after cobalt therapy. Metabolic and hemodynamic abnormalities were corrected equally by ANG II blockade and HIF therapies. However, the molecular patterns differed significantly between ANG II blockade and cobalt therapy. HIF induction may prove to be protective in this model of CKD.

Overexpression of Heme Oxygenase-1 Promotes Osteoblast Differentiation of Osteoporosis Rat Bone Marrow Stromal Cells in Bone Morphogenetic Protein-Dependent Manner

2019 ◽  
Vol 9 (11) ◽  
pp. 1614-1620
Author(s):  
Jiangrong Fan ◽  
Yong Zheng ◽  
Jingyang You
Keyword(s):  
Cell Proliferation ◽  
Real Time ◽  
Heme Oxygenase ◽  
Real Time Pcr ◽  
Osteoblast Differentiation ◽  
Caspase 3 ◽  
Control Group ◽  
Heme Oxygenase 1 ◽  
Dependent Manner ◽  
Alp Activity

BMSCs play a role in osteoporosis (OP) and their differentiation can lead to OP progression. Heme oxygenase-1 (HO-1) involves in many diseases, but the effect of HO-1 on osteoblast differentiation of BMSCs in OP rats remains unclear. SD rats were divided into control group and OP group. Rats BMSCs in OP group were cultured in vitro, HO-1 expression was up-regulated by HO-1 agonist hemin, and BMPR inhibitor LDN-19318 was added followed by analysis of HO-1 expression by real time PCR and ELISA, cell proliferation by MTT assay, apoptosis by Caspase 3 activity, BMP-2 expression by Western blot, ALP activity, expression of Runx2 and OC by real time PCR. In OP group, HO-1 expression was significantly decreased, cell proliferation was inhibited, Caspase 3 activity was increased along with decreased ALP activity and expression of Runx2, OC and BMP-2 compared to control (P < 0.05). Up-regulation of HO-1 expression significantly promoted cell proliferation, reduced Caspase 3 activity, increased ALP activity, and expression of Runx2, OC and BMP-2 (P < 0.05). However, inhibition of HO-1 significantly promoted bone differentiation after the addition of BMPR inhibitor LDN-193189 (P < 0.05). HO-1 expression is decreased in BMSCs of OP group rats. Up-regulation of HO-1 promoted BMSCs proliferation in OP rats in BMP-dependent manner, inhibited apoptosis, and promoted osteoblast differentiation.

scholarly journals CO-Releasing Molecule-2 Induces Nrf2/ARE-Dependent Heme Oxygenase-1 Expression Suppressing TNF-α-Induced Pulmonary Inflammation

2019 ◽  
Vol 8 (4) ◽  
pp. 436 ◽  
Author(s):  
Chih-Chung Lin ◽  
Li-Der Hsiao ◽  
Rou-Ling Cho ◽  
Chuen-Mao Yang
Keyword(s):  
Heme Oxygenase ◽  
Inflammatory Responses ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Alveolar Epithelial Cells ◽  
Intercellular Adhesion Molecule ◽  
Ros Generation ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Small Interfering Rnas ◽  
Tnf Α

The upregulation of heme oxygenase-1 (HO-1) by the carbon monoxide-releasing molecule (CORM)-2 may be mediated through the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases [Nox] and reactive oxygen species (ROS) generation, which could provide cytoprotection against various cellular injuries. However, the detailed mechanisms of CORM-2-induced HO-1 expression in human pulmonary alveolar epithelial cells (HPAEpiCs) remain largely unknown. Therefore, we dissected the mechanisms underlying CORM-2-induced HO-1 expression in HPAEpiCs. We found that the administration of mice with CORM-2 attenuated the tumor necrosis factor-alpha (TNF-α)-induced intercellular adhesion molecule-1 (ICAM-1) expression and leukocyte count as revealed by immunohistochemical staining, western blot, real-time polymerase chain reaction (PCR), and cell count. Furthermore, TNF-α-induced ICAM-1 expression associated with monocyte adhesion to HPAEpiCs was attenuated by infection with adenovirus (adv)-HO-1 or incubation with CORM-2. These inhibitory effects of HO-1 were reversed by pretreatment with hemoglobin (Hb). Moreover, CORM-2-induced HO-1 expression was mediated via the phosphorylation of p47phox, c-Src, epidermal growth factor receptor (EGFR), Akt, and NF-E2-related factor 2 (Nrf2), which were inhibited by their pharmacological inhibitors, including diphenyleneiodonium (DPI) or apocynin (APO), ROS [N-acetyl-L-cysteine (NAC)], PP1, AG1478, PI3K (LY294002), or Akt (SH-5), and small interfering RNAs (siRNAs). CORM-2-enhanced Nrf2 expression, and anti-oxidant response element (ARE) promoter activity was also inhibited by these pharmacological inhibitors. The interaction between Nrf2 and AREs was confirmed with a chromatin immunoprecipitation (ChIP) assay. These findings suggest that CORM-2 increases the formation of the Nrf2 and AREs complex and binds with ARE-binding sites via Src, EGFR, and PI3K/Akt, which further induces HO-1 expression in HPAEpiCs. Thus, the HO-1/CO system might suppress TNF-α-mediated inflammatory responses and exert a potential therapeutic strategy in pulmonary diseases.

scholarly journals Heme Oxygenase-1 is Induced in Glia Throughout Brain by Subarachnoid Hemoglobin

1998 ◽  
Vol 18 (3) ◽  
pp. 257-273 ◽  
Author(s):  
Christopher P. Turner ◽  
Marcelle Bergeron ◽  
Paul Matz ◽  
Angelo Zegna ◽  
Linda J. Noble ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Heat Shock ◽  
Western Blot ◽  
Heme Oxygenase ◽  
Heme Proteins ◽  
Brain Regions ◽  
Heme Oxygenase 1 ◽  
Adult Rats ◽  
Normal Rat ◽  
The Brain

The heme oxygenase-1 gene, HO-1, induced by heme, ischemia, and heat shock, metabolizes heme to biliverdin, free iron, and carbon monoxide. Though the distribution of HO-1 has been described in normal rat brain, little is known about how extracellular heme proteins in the subarachnoid space distribute in brain. To address this issue, hemoglobin was injected into the cisterna magna of adult rats. Expression of HO-1 in these animals was compared with saline-injected, BSA-injected, and uninjected controls. Western blot analysis showed that 24 hours after injection oxyhemoglobin increased HO-1 levels approximately four- to fivefold in all brain regions studied compared with saline-injected and BSA-injected controls. In the brain, HO-1 immunoreactivity was evident at 4 hours and peaked at 24 hours after oxyhemoglobin injections, returning to control levels by 4 to 8 days. This HO-1 induction was detected mainly in cells with small, rounded somas bearing two to four truncated processes, a morphology consistent with that of microglia. These cells were double-stained with the microglial marker, OX42, in every brain region examined. It is proposed that subarachnoid hemoglobin may be taken up into microglia wherein heme induces HO-1.

Trilobatin Protects Cardiomyocytes from Hypoxia/ Reperfusion Injury by Regulating the Nuclear Factor Erythroid 2-Related Factor 2/Heme Oxygenase-1 Pathway

2020 ◽  
Vol 19 (2) ◽  
pp. 133-138
Author(s):  
Wenyu Chen ◽  
Hui He
Keyword(s):  
Heme Oxygenase ◽  
Molecular Mechanisms ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Cellular Injury ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
H9c2 Cells ◽  
Natural Plant ◽  
Induced Changes

Trilobatin is a natural plant-derived glycosylated flavonoid that has been shown to exhibit multiple beneficial pharmacologic activities including protection of heart against H/R-induced cardiomyocyte injury. However, the molecular mechanisms underlying protection from H/R-induced cardiomyocyte injury remain unknown. Using H9C2 cells as a model, we examined the effect of trilobatin on H/R-induced cellular injury, apoptosis, and generation of reactive oxygen species. The results showed that trilobatin protected H9C2 cells not only from cell death and apoptosis, but also counteracted H/R-induced changes in malondialdehyde, superoxide dismutase, glutathione, and glutathione peroxidase. The evaluation of the mechanism underlying the effect of trilobatin on protection from H/R-induced cellular injury suggested changes in the regulation of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway.

RPS24c Isoform Facilitates Tumor Angiogenesis Via Promoting the Stability of MVIH in Colorectal Cancer

2020 ◽  
Vol 20 (5) ◽  
pp. 388-395 ◽  
Author(s):  
Yue Wang ◽  
Youjun Wu ◽  
Kun Xiao ◽  
Yingjie Zhao ◽  
Gang Lv ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Ribosomal Protein ◽  
Real Time ◽  
Tumor Angiogenesis ◽  
Real Time Pcr ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Binding Interaction ◽  
Tubule Formation ◽  
The Stability

Background: Colorectal cancer (CRC) is the second leading cause of death worldwide, and distant metastasis is responsible for the poor prognosis in patients with advanced-stage CRC. RPS24 (ribosomal protein S24) as a ribosomal protein, multiple transcript variant encoding different isoforms have been found for this gene. Our previous studies have demonstrated that RPS24 is overexpressed in CRC. However, the mechanisms underlying the role of RPS24 in tumor development have not been fully defined. Methods: Expression of RPS24 isoforms and lncRNA MVIH in CRC tissues and cell lines were quantified by real-time PCR or western blotting assay. Endothelial tube formation assay was performed to determine the effect of RPS24 on tumor angiogenesis. The cell viability of HUVEC was determined by MTT assay, and the migration and invasion ability of HUVEC were detected by transwell assay. PGK1 secretion was tested with a specific ELISA kit. Results: Here, we found that RPS24c isoform was a major contributor to tumor angiogenesis, a vital process in tumor growth and metastasis. Real-time PCR revealed that RPS24c isoform was highly expressed in CRC tissues, while other isoforms are present in both normal and CRC tissues with no statistical difference. Moreover the change of RPS24 protein level is mainly due to the fluctuation of RPS24c. Furthermore, we observed that silencing RPS24c could decrease angiogenesis by inhibiting tubule formation, HUVEC cell proliferation and migration. Additionally, we investigated the molecular mechanisms and demonstrated that RPS24c mRNA interacted with lncRNA MVIH, the binding-interaction enhanced the stability of each other, thereby activated angiogenesis by inhibiting the secretion of PGK1. Conclusion: RPS24c facilitates tumor angiogenesis via the RPS24c/MVIH/PGK1 pathway in CRC. RPS24c inhibition may be a novel option for anti-vascular treatment in CRC.

scholarly journals KLK11 promotes the activation of mTOR and protein synthesis to facilitate cardiac hypertrophy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yi Wang ◽  
Hongjuan Liao ◽  
Yueheng Wang ◽  
Jinlin Zhou ◽  
Feng Wang ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Western Blot ◽  
Real Time ◽  
Real Time Pcr ◽  
Mtor Signaling ◽  
Heart Weight ◽  
Cardiomyocyte Hypertrophy ◽  
Quantitative Real Time Pcr

Abstract Background Cardiovascular diseases have become the leading cause of death worldwide, and cardiac hypertrophy is the core mechanism underlying cardiac defect and heart failure. However, the underlying mechanisms of cardiac hypertrophy are not fully understood. Here we investigated the roles of Kallikrein 11 (KLK11) in cardiac hypertrophy. Methods Human and mouse hypertrophic heart tissues were used to determine the expression of KLK11 with quantitative real-time PCR and western blot. Mouse cardiac hypertrophy was induced by transverse aortic constriction (TAC), and cardiomyocyte hypertrophy was induced by angiotensin II. Cardiac function was analyzed by echocardiography. The signaling pathway was analyzed by western blot. Protein synthesis was monitored by the incorporation of [3H]-leucine. Gene expression was analyzed by quantitative real-time PCR. Results The mRNA and protein levels of KLK11 were upregulated in human hypertrophic hearts. We also induced cardiac hypertrophy in mice and observed the upregulation of KLK11 in hypertrophic hearts. Our in vitro experiments demonstrated that KLK11 overexpression promoted whereas KLK11 knockdown repressed cardiomyocytes hypertrophy induced by angiotensin II, as evidenced by cardiomyocyte size and the expression of hypertrophy-related fetal genes. Besides, we knocked down KLK11 expression in mouse hearts with adeno-associated virus 9. Knockdown of KLK11 in mouse hearts inhibited TAC-induced decline in fraction shortening and ejection fraction, reduced the increase in heart weight, cardiomyocyte size, and expression of hypertrophic fetal genes. We also observed that KLK11 promoted protein synthesis, the key feature of cardiomyocyte hypertrophy, by regulating the pivotal machines S6K1 and 4EBP1. Mechanism study demonstrated that KLK11 promoted the activation of AKT-mTOR signaling to promote S6K1 and 4EBP1 pathway and protein synthesis. Repression of mTOR with rapamycin blocked the effects of KLK11 on S6K1 and 4EBP1 as well as protein synthesis. Besides, rapamycin treatment blocked the roles of KLK11 in the regulation of cardiomyocyte hypertrophy. Conclusions Our findings demonstrated that KLK11 promoted cardiomyocyte hypertrophy by activating AKT-mTOR signaling to promote protein synthesis.

scholarly journals Heme oxygenase-1 and carbon monoxide in pulmonary medicine

2003 ◽  
Vol 4 (1) ◽  
Author(s):  
Dirk-Jan Slebos ◽  
Stefan W Ryter ◽  
Augustine MK Choi
Keyword(s):  
Carbon Monoxide ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Pulmonary Medicine
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