Metoprolol Protects Against Arginine Vasopressin-Induced Cellular Senescence in H9C2 Cardiomyocytes by Regulating the Sirt1/p53/p21 Axis

AbstractCardiomyocyte senescence is involved in the pathological mechanism of cardiac diseases. Metoprolol is a β1 receptor blocker used for the treatment of hypertension. Recent studies show that Metoprolol can protect cardiomyocytes against ischemia injury. The present study aims to investigate the protective effects of Metoprolol against arginine vasopressin (AVP)-induced cellular senescence in cultured cardiomyocytes. The cell proliferation assay and cytotoxicity lactate dehydrogenase assay showed that the highest tolerated dosage of Metoprolol in H9C2 cardiomyocytes was optimized as 10 µM. The enzyme-linked immunosorbent assay showed that Metoprolol significantly ameliorated the elevated level of the DNA oxidation product 8-hydroxy-2 deoxyguanosine. Metoprolol also decreased the percentage of senescence-associated β-galactosidase positive cells and improved the telomerase activity under AVP exposure. Moreover, treatment with Metoprolol ameliorated the decreased intracellular nicotinamide phosphoribosyltransferase activity, nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NAD+/NADPH) ratio, and Sirtuin1 activity in cardiomyocytes by AVP. Finally, Metoprolol was able to downregulate the AVP-induced expression of acetylated p53 and p21. Taken together, our data reveal that Metoprolol protected the cardiomyocytes from AVP-induced senescence.

Download Full-text

The Protective Effects of Metoprolol Against Arginine Vasopressin (AVP)-Induced Cellular Senescence in Cardiomyocytes

10.21203/rs.3.rs-389371/v1 ◽

2021 ◽

Author(s):

Qiang Li ◽

Kang Huang ◽

Tianyi Ma ◽

Shijuan Lu ◽

Shilin Tang ◽

...

Keyword(s):

Cellular Senescence ◽

Arginine Vasopressin ◽

Elevated Level ◽

Telomerase Activity ◽

Cell Senescence ◽

Protective Effects ◽

Rt Pcr ◽

Pathological Mechanism ◽

Treatment Of Hypertension ◽

Commercial Kits

Abstract Cellular senescence of cardiomyocytes is reported to be involved in the pathological mechanism of cardiac diseases. Metoprolol is a blocker of β1 receptor used for the treatment of hypertension, which is recently reported to protect cardiomyocytes from injury. The present study aims to investigate the protective effects of Metoprolol against Arginine vasopressin (AVP)-induced cellular senescence in cardiomyocytes. CCK-8 and LDH release assays were used to evaluate cytotoxicity. ELISA was used to detect the release of 8OHdG. SA-β-gal activity and telomerase activity were measured to index cell senescence. The iNampt activity, NAD+/NADPH ratio, and Sirt1 activity were detected by commercial kits. Levels of acetylated p53 were measured by immunoprecipitation and the expression of p21 was determined by RT-PCR and western blot analysis. We found that the elevated level of 8OHdG, percentage of SA-β-gal positive cells, and decreased telomerase activity induced by AVP were significantly reversed by the treatment of Metoprolol. Metoprolol elevated the suppressed iNampt activity, NAD+/NADPH ratio, and Sirt1 activity in cardiomyocytes challenged with AVP. The upregulated expression of acetylated p53 and p21 induced by AVP were dramatically downregulated by the presence of Metoprolol. Taken together, our data revealed that Metoprolol protected the cell senescence in cardiomyocytes induced by AVP.

Download Full-text

Extracellular glutathione inhibits oxygen-induced permeability changes in alveolar epithelial monolayers

Journal of Applied Physiology ◽

10.1152/jappl.2001.91.2.748 ◽

2001 ◽

Vol 91 (2) ◽

pp. 748-754 ◽

Cited By ~ 13

Author(s):

J. H. Roum ◽

A. S. Aledia ◽

L. A. Carungcong ◽

K.-J. Kim ◽

Z. Borok

Keyword(s):

Glutathione Reductase ◽

Nicotinamide Adenine Dinucleotide ◽

Clinical Manifestations ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Alveolar Epithelium ◽

Oxygen Toxicity ◽

Nicotinamide Adenine ◽

Protective Effects ◽

Alveolar Epithelial ◽

Active Ion Transport

Exposure to high fractional inspired oxygen for 24 h increases permeability of the alveolar epithelium, contributing to the clinical manifestations of oxygen toxicity. Utilizing a model of the alveolar epithelium in which isolated rat type II cells form polarized monolayers on polycarbonate filters [transepithelial resistance ( R t) > 1 kΩ · cm2 by day 4], we evaluated the ability of reduced glutathione (GSH) to ameliorate these changes. On day 4, apical fluid was replaced with culture medium containing 1) no additives, 2) GSH (500 μM), or 3) GSH (500 μM) + glutathione reductase (0.5 U/ml) + nicotinamide adenine dinucleotide phosphate (250 μM). Monolayers were exposed (for 24 h) to room air (control) or 95% O2, each containing 5% CO2. After 24 h of hyperoxia, R t for condition 1decreased by 45% compared with control ( P < 0.001). In conditions 2 and 3, R tdid not decrease significantly ( P = not significant). Hyperoxia-induced decreases in active ion transport were observed for conditions 1 and 2 ( P < 0.05), but not for condition 3 ( P = not significant). These findings indicate that extracellular GSH may protect the alveolar epithelium against hyperoxia-induced injury. Addition of glutathione reductase and nicotinamide adenine dinucleotide phosphate may further augment these protective effects of GSH.

Download Full-text

Effect of Niacin on Mitochondria of Allium Cepa Root Cells

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100060404 ◽

1967 ◽

Vol 25 ◽

pp. 78-79

Author(s):

M. Arif Hayat

Keyword(s):

Nicotinamide Adenine Dinucleotide ◽

Hydrogen Transfer ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Nicotinamide Adenine ◽

Root Tips ◽

Root Cells ◽

Transfer Processes ◽

Standard Procedures ◽

A Cell ◽

Critical Interest

Although it is recognized that niacin (pyridine-3-carboxylic acid), incorporated as the amide in nicotinamide adenine dinucleotide (NAD) or in nicotinamide adenine dinucleotide phosphate (NADP), is a cofactor in hydrogen transfer in numerous enzyme reactions in all organisms studied, virtually no information is available on the effect of this vitamin on a cell at the submicroscopic level. Since mitochondria act as sites for many hydrogen transfer processes, the possible response of mitochondria to niacin treatment is, therefore, of critical interest.Onion bulbs were placed on vials filled with double distilled water in the dark at 25°C. After two days the bulbs and newly developed root system were transferred to vials containing 0.1% niacin. Root tips were collected at ¼, ½, 1, 2, 4, and 8 hr. intervals after treatment. The tissues were fixed in glutaraldehyde-OsO4 as well as in 2% KMnO4 according to standard procedures. In both cases, the tissues were dehydrated in an acetone series and embedded in Reynolds' lead citrate for 3-10 minutes.

Download Full-text