Overexpression of ankyrin repeat domain 1 enhances cardiomyocyte apoptosis by promoting p53 activation and mitochondrial dysfunction in rodents

2015 ◽  
Vol 128 (10) ◽  
pp. 665-678 ◽  
Author(s):  
Liang Shen ◽  
Ci Chen ◽  
Xuan Wei ◽  
Xixian Li ◽  
Guangjin Luo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Mitochondrial Dysfunction ◽  
Cell Apoptosis ◽  
Pressure Overload ◽  
Ankyrin Repeat ◽  
Cardiomyocyte Apoptosis ◽  
Repeat Domain ◽  
Ankyrin Repeat Domain ◽  
P53 Activation

This study demonstrated that myocardial overexpression of Ankrd1/CARP promotes angiotensin-II- and pressure-overload-induced cell apoptosis and heart failure, with these deleterious effects being at least partly mediated by the accumulation of p53 and mitochondrial dysfunction.

scholarly journals Asparaginyl Hydroxylation of the Notch Ankyrin Repeat Domain by Factor Inhibiting Hypoxia-inducible Factor

2007 ◽  
Vol 282 (33) ◽  
pp. 24027-24038 ◽  
Author(s):  
Mathew L. Coleman ◽  
Michael A. McDonough ◽  
Kirsty S. Hewitson ◽  
Charlotte Coles ◽  
Jasmin Mecinović ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Ankyrin Repeat ◽  
Repeat Domain ◽  
Ankyrin Repeat Domain

scholarly journals Oxidative Stress as A Mechanism for Functional Alterations in Cardiac Hypertrophy and Heart Failure

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 931
Author(s):  
Anureet K. Shah ◽  
Sukhwinder K. Bhullar ◽  
Vijayan Elimban ◽  
Naranjan S. Dhalla
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Cardiac Remodeling ◽  
Cardiac Dysfunction ◽  
Critical Role ◽  
Pressure Overload ◽  
Hypertrophied Heart ◽  
Vasoactive Hormones

Although heart failure due to a wide variety of pathological stimuli including myocardial infarction, pressure overload and volume overload is associated with cardiac hypertrophy, the exact reasons for the transition of cardiac hypertrophy to heart failure are not well defined. Since circulating levels of several vasoactive hormones including catecholamines, angiotensin II, and endothelins are elevated under pathological conditions, it has been suggested that these vasoactive hormones may be involved in the development of both cardiac hypertrophy and heart failure. At initial stages of pathological stimuli, these hormones induce an increase in ventricular wall tension by acting through their respective receptor-mediated signal transduction systems and result in the development of cardiac hypertrophy. Some oxyradicals formed at initial stages are also involved in the redox-dependent activation of the hypertrophic process but these are rapidly removed by increased content of antioxidants in hypertrophied heart. In fact, cardiac hypertrophy is considered to be an adaptive process as it exhibits either normal or augmented cardiac function for maintaining cardiovascular homeostasis. However, exposure of a hypertrophied heart to elevated levels of circulating hormones due to pathological stimuli over a prolonged period results in cardiac dysfunction and development of heart failure involving a complex set of mechanisms. It has been demonstrated that different cardiovascular abnormalities such as functional hypoxia, metabolic derangements, uncoupling of mitochondrial electron transport, and inflammation produce oxidative stress in the hypertrophied failing hearts. In addition, oxidation of catecholamines by monoamine oxidase as well as NADPH oxidase activation by angiotensin II and endothelin promote the generation of oxidative stress during the prolonged period by these pathological stimuli. It is noteworthy that oxidative stress is known to activate metallomatrix proteases and degrade the extracellular matrix proteins for the induction of cardiac remodeling and heart dysfunction. Furthermore, oxidative stress has been shown to induce subcellular remodeling and Ca2+-handling abnormalities as well as loss of cardiomyocytes due to the development of apoptosis, necrosis, and fibrosis. These observations support the view that a low amount of oxyradical formation for a brief period may activate redox-sensitive mechanisms, which are associated with the development of cardiac hypertrophy. On the other hand, high levels of oxyradicals over a prolonged period may induce oxidative stress and cause Ca2+-handling defects as well as protease activation and thus play a critical role in the development of adverse cardiac remodeling and cardiac dysfunction as well as progression of heart failure.

Hexarelin protects rat cardiomyocytes from angiotensin II-induced apoptosis in vitro

2004 ◽  
Vol 286 (3) ◽  
pp. H1063-H1069 ◽  
Author(s):  
Jin-Jiang Pang ◽  
Rong-Kun Xu ◽  
Xiang-Bin Xu ◽  
Ji-Min Cao ◽  
Chao Ni ◽  
...  
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Caspase 3 ◽  
Cardiomyocyte Apoptosis ◽  
Protective Effects ◽  
Ang Ii ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Rat Cardiomyocytes ◽  
Induced Apoptosis

Loss of cardiomyocytes by apoptosis is proposed to cause heart failure. Angiotensin II (ANG II), an important neurohormonal factor during heart failure, can induce cardiomyocyte apoptosis. Inasmuch as hexarelin has been reported to have protective effects in this process, we examined whether hexarelin can prevent cardiomyocytes from ANG II-induced cell death. Cultured cardiomyocytes from neonatal rats were stimulated with ANG II. Apoptosis was evaluated using fluorescence microscopy, TdT-mediated dUTP nick-end labeling (TUNEL) method, flow cytometry, DNA laddering, and analysis of cell viability by (3,4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). It was found that incubation with 0.1 μmol/l ANG II for 48 h increased cardiomyocyte apoptosis. Administration of 0.1 μmol/l hexarelin significantly decreased this ANG II-induced apoptosis and DNA fragmentation and increased myocyte viability. To further investigate the underlying mechanisms, caspase-3 activity assay and mRNA expression of Bax, Bcl-2, and growth hormone secretagogue receptor (GHS-R; the supposed hexarelin binding site) were examined. GHS-R mRNA was abundantly expressed in cardiomyocytes and was upregulated after administration of hexarelin. These results suggest that hexarelin abates cardiomyocytes from ANG II-induced apoptosis possibly via inhibiting the increased caspase-3 activity and Bax expression induced by ANG II and by increasing the expression of Bcl-2, which is depressed by ANG II. Whether the upregulated expression of GHS-R induced by hexarelin is associated with this antiapoptotic effect deserves further investigation.

FIH-Dependent Asparaginyl Hydroxylation of Ankyrin Repeat Domain-Containing Proteins

2009 ◽  
Vol 1177 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Matthew E. Cockman ◽  
James D. Webb ◽  
Peter J. Ratcliffe
Keyword(s):  
Ankyrin Repeat ◽  
Repeat Domain ◽  
Ankyrin Repeat Domain

scholarly journals Clinical significance of Ankyrin repeat domain 12 expression in colorectal cancer

2013 ◽  
Vol 32 (1) ◽  
pp. 35 ◽  
Author(s):  
Rui Bai ◽  
Dan Li ◽  
Zhong Shi ◽  
Xuefeng Fang ◽  
Weiting Ge ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Significance ◽  
Ankyrin Repeat ◽  
Repeat Domain ◽  
Ankyrin Repeat Domain

scholarly journals Ankyrin Repeat Domain 1 Overexpression is Associated with Common Resistance to Afatinib and Osimertinib in EGFR-mutant Lung Cancer

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Akiko Takahashi ◽  
Masahiro Seike ◽  
Mika Chiba ◽  
Satoshi Takahashi ◽  
Shinji Nakamichi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Ankyrin Repeat ◽  
Repeat Domain ◽  
Ankyrin Repeat Domain ◽  
Egfr Mutant

scholarly journals Calcium activates purified human TRPA1 with and without its N-terminal ankyrin repeat domain in the absence of calmodulin

Cell Calcium ◽  
2020 ◽  
Vol 90 ◽  
pp. 102228 ◽  
Author(s):  
Lavanya Moparthi ◽  
Satish Babu Moparthi ◽  
Jérôme Wenger ◽  
Peter M. Zygmunt
Keyword(s):  
Ankyrin Repeat ◽  
Repeat Domain ◽  
Ankyrin Repeat Domain

scholarly journals Visualization of the nanospring dynamics of the I B  ankyrin repeat domain in real time

2011 ◽  
Vol 108 (25) ◽  
pp. 10178-10183 ◽  
Author(s):  
J. A. Lamboy ◽  
H. Kim ◽  
K. S. Lee ◽  
T. Ha ◽  
E. A. Komives
Keyword(s):  
Real Time ◽  
Ankyrin Repeat ◽  
Repeat Domain ◽  
Ankyrin Repeat Domain
Sign in / Sign up

Export Citation Format

Share Document