alexa β-Adrenergic Receptor Signaling Regulates rAAV Transduction through Calcineurin in Heart Muscle Cells | OMICS International | Abstract
ISSN: 2157-7412

Journal of Genetic Syndromes & Gene Therapy
Open Access

Like us on:

OMICS International organises 3000+ Global Conferenceseries Events every year across USA, Europe & Asia with support from 1000 more scientific Societies and Publishes 700+ Open Access Journals which contains over 50000 eminent personalities, reputed scientists as editorial board members.

Open Access Journals gaining more Readers and Citations
700 Journals and 15,000,000 Readers Each Journal is getting 25,000+ Readers

This Readership is 10 times more when compared to other Subscription Journals (Source: Google Analytics)

Research Article

β-Adrenergic Receptor Signaling Regulates rAAV Transduction through Calcineurin in Heart Muscle Cells

Andrew Natonson1, Jarrod Dean1, Masaaki Ii1, Atsushi Iwakura1, Jeremy Plante1, Ulrike Mende2, Jarrod S. Johnson3, R. Jude Samulski3, John E. J. Rasko4,5 and Ryuichi Aikawa1,4*

1Cardiovascular Research, St. Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02135, USA

2Cardiovascular Research Center, Rhode Island Hospital & Brown Medical School, Providence, RI 02903, USA

3Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7352, USA

4Gene and Stem Cell Therapy, Centenary Institute, University of Sydney, Newtown, NSW2042, Australia

5Cell and Molecular Therapies, Royal Prince Alfred Hospital, Camperdown, NSW 2050

*Corresponding Author:
Ryuichi Aikawa MD
PhD, Kuwana City Hospital
1-32-1 Chuo-cho, Kuwana city
Mie 511-0068, Japan
Tel: +81-594-22-0650
Fax: +81-594-22-5608
E-mail: [email protected]

Received date: December 11, 2010; Accepted date:January 12, 2011; Published date: January 16, 2011

Citation: Natonson A, Dean J, Li M, Iwakura A, Plante J, et al. (2010) ß-Adrenergic Receptor Signaling Regulates rAAV Transduction through Calcineurin in Heart Muscle Cells. J Genet Syndr Gene Ther 1:102. doi:10.4172/2157-7412.1000102

Copyright: © 2010 Natonson A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Recombinant adeno-associated virus (rAAV)-based gene therapy represents a promising approach for the treatment of heart muscle diseases, but the molecular mechanisms that direct rAAV transduction remain unclear. Here we demonstrate that ?-adrenergic receptor stimulation with isoproterenol (ISO) markedly increased cardiomyocyte transduction of rAAV in vitro and in vivo. Conversely, chronic ?-adrenergic receptor downregulation significantly suppressed rAAV transduction. Pretreatment with calcium signaling cascade inhibitors including calcineurin inhibitory peptide (CNIP) strongly suppressed the positive effects of ISO on rAAV transduction. Additionally we document that ISO treatment led to a significant increase in double-stranded (ds) DNA synthesis of the rAAV genome and an increase in promoter activity. Moreover, stimulation with ISO did not affect rAAV transduction in calcineurin nullizygous mice. Collectively, we conclude that a calcium-dependent pathway regulates rAAV vector transduction at a number of stages that may include vector mobilization, conversion, and transcription activity. Modulating this pathway through ?-adrenergic signaling enhances rAAV-mediated gene delivery to cardiomyocytes, and may be valuable when considering therapeutic approaches for heart muscle diseases.

Keywords

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2018-19
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

[email protected]

+1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001Extn: 9042

 
© 2008- 2018 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
Leave Your Message 24x7