Arachidonic Acid–Dependent Activation of a p22phox-Based NAD(P)H Oxidase Mediates Angiotensin II–Induced Mesangial Cell Protein Synthesis and Fibronectin Expression via Akt/PKB

2006 ◽  
Vol 8 (9-10) ◽  
pp. 1497-1508 ◽  
Author(s):  
Karen Block ◽  
Jill M. Ricono ◽  
Duck–Yoon Lee ◽  
Basant Bhandari ◽  
Goutam Ghosh Choudhury ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Arachidonic Acid ◽  
Angiotensin Ii ◽  
Mesangial Cell ◽  
Cell Protein ◽  
Fibronectin Expression

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 Somatostatin antagonizes angiotensin II effects on mesangial cell contraction and glomerular filtration

1993 ◽  
Vol 43 (2) ◽  
pp. 324-333 ◽  
Author(s):  
Carmen García-Escribano ◽  
Maria Luisa Díez-Marqués ◽  
Mercedes González-Rubio ◽  
Manuel Rodríguez-Puyol ◽  
Diego Rodríguez-Puyol
Keyword(s):  
Angiotensin Ii ◽  
Glomerular Filtration ◽  
Mesangial Cell ◽  
Cell Contraction

scholarly journals Evidence for mesangial glomerular receptors for angiotensin II linked to mesangial cell contractility

FEBS Letters ◽  
1980 ◽  
Vol 121 (2) ◽  
pp. 333-339 ◽  
Author(s):  
J. Foidart ◽  
J. Sraer ◽  
F. Delarue ◽  
P. Mahieu ◽  
R. Ardaillou
Keyword(s):  
Angiotensin Ii ◽  
Mesangial Cell ◽  
Cell Contractility

Involvement of Arachidonic Acid Metabolism in Insulin-stimulated Protein Synthesis in Cultured L6 Myocytes

1991 ◽  
Vol 55 (6) ◽  
pp. 1449-1453
Author(s):  
Kazumi Yagasaki ◽  
Kouichi Saito ◽  
Michihito Yamaguchi ◽  
Ryuhei Funabiki
Keyword(s):  
Protein Synthesis ◽  
Arachidonic Acid ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
L6 Myocytes

P-450 Metabolites of Arachidonic Acid in the Control of Cardiovascular Function

2002 ◽  
Vol 82 (1) ◽  
pp. 131-185 ◽  
Author(s):  
Richard J. Roman
Keyword(s):  
Arachidonic Acid ◽  
Angiotensin Ii ◽  
Vascular Tone ◽  
Mesangial Cells ◽  
Cardiovascular Function ◽  
Tubuloglomerular Feedback ◽  
Peripheral Vasculature ◽  
Therapeutic Benefits

Recent studies have indicated that arachidonic acid is primarily metabolized by cytochrome P-450 (CYP) enzymes in the brain, lung, kidney, and peripheral vasculature to 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs) and that these compounds play critical roles in the regulation of renal, pulmonary, and cardiac function and vascular tone. EETs are endothelium-derived vasodilators that hyperpolarize vascular smooth muscle (VSM) cells by activating K+channels. 20-HETE is a vasoconstrictor produced in VSM cells that reduces the open-state probability of Ca2+-activated K+channels. Inhibitors of the formation of 20-HETE block the myogenic response of renal, cerebral, and skeletal muscle arterioles in vitro and autoregulation of renal and cerebral blood flow in vivo. They also block tubuloglomerular feedback responses in vivo and the vasoconstrictor response to elevations in tissue Po2both in vivo and in vitro. The formation of 20-HETE in VSM is stimulated by angiotensin II and endothelin and is inhibited by nitric oxide (NO) and carbon monoxide (CO). Blockade of the formation of 20-HETE attenuates the vascular responses to angiotensin II, endothelin, norepinephrine, NO, and CO. In the kidney, EETs and 20-HETE are produced in the proximal tubule and the thick ascending loop of Henle. They regulate Na+transport in these nephron segments. 20-HETE also contributes to the mitogenic effects of a variety of growth factors in VSM, renal epithelial, and mesangial cells. The production of EETs and 20-HETE is altered in experimental and genetic models of hypertension, diabetes, uremia, toxemia of pregnancy, and hepatorenal syndrome. Given the importance of this pathway in the control of cardiovascular function, it is likely that CYP metabolites of arachidonic acid contribute to the changes in renal function and vascular tone associated with some of these conditions and that drugs that modify the formation and/or actions of EETs and 20-HETE may have therapeutic benefits.

Increased extracellular matrix synthesis and mRNA in mesangial cells grown in high-glucose medium

1991 ◽  
Vol 260 (2) ◽  
pp. F185-F191 ◽  
Author(s):  
S. H. Ayo ◽  
R. A. Radnik ◽  
W. F. Glass ◽  
J. A. Garoni ◽  
E. R. Rampt ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Protein Synthesis ◽  
High Glucose ◽  
Mesangial Cells ◽  
Matrix Proteins ◽  
Cell Protein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Glomerular Mesangial Cells ◽  
Glomerular Mesangium

Nodular expansion of glomerular mesangium with increased amounts of extracellular matrix (ECM) material is pathognomic of diabetic nephropathy. The precise mechanisms involved in this accumulation are unknown. Recently, we reported using a solid-phase enzyme-linked immunosorbent assay (ELISA) technique that glomerular mesangial cells, the principal cell type residing in glomerular mesangium, accumulate 50–60% more fibronectin (FN), laminin (LM), and type IV collagen (T-IV) when cultured in medium containing high glucose (30 mM) (S. H. Ayo, R. A. Rodnik, J. Garoni, W. F. Glass II, and J. I. Kreiberg. Am. J. Pathol. 136: 1339-1348, 1990). ECM assembly is controlled by its rate of synthesis and degradation, as well as its binding and rate of incorporation into the ECM. To elucidate the mechanisms involved, pulse-chase experiments were designed to estimate ECM protein synthesis from the incorporation of Trans-35S [( 35S]methionine, [35S]cysteine) into immunoprecipitated FN, LM, and T-IV. mRNA levels were examined, and degradation rates were estimated from the disappearance of radioactivity from matrix proteins in mesangial cells previously incubated with Trans-35S. One week of growth in 30 mM glucose resulted in approximately 40–50% increase in the synthesis of all three matrix proteins compared with 10 mM glucose-grown cells. This was accompanied by a significant increase in the transcripts for all three matrix proteins (approximately twofold). The specific activity of the radiolabel in trichloroacetic acid-precipitable cell protein showed no difference between cells grown in 10 or 30 mM glucose, indicating that total protein synthesis was unchanged. After 1 wk, the rate of FN, LM, and T-IV collagen degradation was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Inhibition of Host Protein Synthesis and Degradation of Cellular mRNAs During Infection by Influenza and Herpes Simplex Virus

1982 ◽  
Vol 2 (12) ◽  
pp. 1644-1648 ◽  
Author(s):  
S. C. Inglis
Keyword(s):  
Protein Synthesis ◽  
Blot Hybridization ◽  
Host Protein ◽  
Cell Protein ◽  
Cellular Genes ◽  
Cellular Mrnas ◽  
The Stability ◽  
Simplex Virus ◽  
Host Protein Synthesis ◽  
Synthesis And Degradation

Cloned DNA copies of two cellular genes were used to monitor, by blot hybridization, the stability of particular cell mRNAs after infection by influenza virus and herpesvirus. The results indicated that the inhibition of host cell protein synthesis that accompanied infection by each virus could be explained by a reduction in the amounts of cellular mRNAs in the cytoplasm, and they suggested that this decrease was due to virus-mediated mRNA degradation.

Sign in / Sign up

Export Citation Format

Share Document