alexa
ISSN: 2155-9589
Journal of Membrane Science & Technology
Like us on:
Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

Essential Role of Phospholipase C-g1 in Hypoxia-Induced Pulmonary Vasoconstriction and Hypertension

Vishal R Yadav, Yun-Min Zheng and Yong-Xiao Wang*

Center for Cardiovascular Sciences, Albany Medical College, Albany, New York, USA

*Corresponding Author:
Dr. Yong-Xiao Wang
Center for Cardiovascular Sciences
Albany Medical College, Albany, New York, USA
E-mail: wangy@mail.amc.edu

Received date June 13, 2013; Accepted date June 16, 2013; Published date June 18, 2013

Citation: Yadav VR, Zheng YM, Wang YX (2013) Essential Role of Phospholipase C-g1 in Hypoxia-Induced Pulmonary Vasoconstriction and Hypertension. J Membra Sci Technol 3:e115. doi:10.4172/2155-9589.1000e115

Copyright: © 2013 Yadav VR, 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.

Visit for more related articles at Journal of Membrane Science & Technology

Hypoxia-induced Pulmonary Vasoconstriction (HPV) is an essential physiological process which ensures proper ventilationperfusion matching in pulmonary circulation with the ultimate aim of optimizing systemic oxygen delivery. However, this cellular response can become a key pathological process leading to pulmonary artery hypertension and right heart failure. An increase in intracellular calcium concentration ([Ca2+]i) in Pulmonary Artery Smooth Muscle Cells (PASMCs) plays a crucial role in producing HPV. However, the underlying signaling mechanisms are not completely understood [1-3]. Thus, the identification of the molecular players involved in HPV is imperative for a deeper and broader understanding of hypoxic pulmonary artery hypertension and other related diseases.

Phospholipase C (PLC) is a key enzyme family for numerous physiological and pathological cellular responses in the cardiovascular system. On activation, PLC hydrolyses the plasma membranebound phosphatidylinositol bisphosphate (PIP2) into inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 opens IP3 receptors (IP3Rs) on the Sarcoplasmic Reticulum (SR) membrane to induce Ca2+ release. DAG activates protein kinase C to lead Ca2+- dependent cellular responses. Among all known isoforms, PLCγ1 has shown to be highly expressed in the lungs [4], and involved in reactive oxygen species (ROS)-evoked increase in [Ca2+]i in PC-12 cell line [5], cultured human venous SMCs [6] and cultured rat astrocytes [7]. ROS are known to be critical for the hypoxic increase in [Ca2+]i in PAMSCs [1,8]. Taken together, it was conjectured that PLCγ1 would be a major regulator in the hypoxic increase in [Ca2+]i in PASMCs and HPV.

We conducted a series of experiments to test the aforementioned exciting assumption. Our data have revealed that PLCγ1 is activated in pulmonary arteries following acute hypoxic exposure. Equally importantly, lentiviral shRNA-mediated knock-down of PLCγ1 or pharmacological inhibition of PLC significantly reduces hypoxiainduced increase in [Ca2+]i in PASMCs and HPV [9]. It is interesting to note that PLCγ1 enhances survival of MEF cells [10] and cardiomycytes during oxidative stress [11]. Patterson and coworkers have reported that PLCγ is required for agonist-induced Ca2+ entry in PC12 and A7r5 cells by controlling TRPC3 trafficking and expression on the plasma membrane [12,13]. Homozygous PLCγ1 gene knockout mice show the early embryonic lethality [14], further reinforcing the functional importance of PLCγ1.

Our very recent studies have further unveiled that acute hypoxic exposure causes significant phosphorylation of PLCγ1 at tyrosine 783, which is regarded as vital for activation of PLCγ1 [15], in PASMCs [9]. Gene silencing of Rieske Iron-Sulfur Protein (RISP) to inhibit ROS generation at the mitochondrial complex III [8] fully abolishes the acute hypoxic phosphorylation of PLCγ1 [9]. Similarly, treatment with the mitochondrial complex III inhibitor myxothiazol to block ROS generation [16-18] completely inhibits the hypoxic response as well. Collectively, the hypoxic activation of PLCγ1 in PASMCs is mediated by RISP-dependent mitochondrial ROS production. Whether or not hypoxic activation of PLCγ1 is directly dependent on ROS or ROS mediated interplay molecules is a matter of further investigation. Nevertheless, targeting PLCγ1 on the plasma membrane may provide a viable and important approach in developing new and more effective therapeutic strategies for hypoxic pulmonary artery hypertension and other related diseases.

References

Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Relevant Topics

Recommended Conferences

  • 14th International Conference on Nanomaterials and Nanotechnology
    March 30- 31, 2017 Madrid, Spain
  • 1st World Congress on Nano Science and Nano Technology
    July 10-11, 2017 Jakarta, Indonesia
  • Annual Meeting on Separation Techniques
    July 12-14, 2017 bangkok, Thailand
  • Biotechnology Congress
    July 17-19, 2017 Kualalumpur, Malaysia
  • 2nd International Conference and Expo on Water Microbiology & Novel Technologies
    (10 Plenary Forums 3 days 1 Event)
    August 28-30, 2017, Philadelphia, USA

Article Usage

  • Total views: 11350
  • [From(publication date):
    September-2013 - Dec 05, 2016]
  • Breakdown by view type
  • HTML page views : 7607
  • PDF downloads :3743
 

Post your comment

captcha   Reload  Can't read the image? click here to refresh

OMICS International Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
 
 
OMICS International Conferences 2016-17
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings
 
 

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

agrifoodaquavet@omicsonline.com

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

clinical_biochem@omicsonline.com

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

business@omicsonline.com

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

chemicaleng_chemistry@omicsonline.com

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

environmentalsci@omicsonline.com

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

engineering@omicsonline.com

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

generalsci_healthcare@omicsonline.com

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

genetics_molbio@omicsonline.com

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

immuno_microbio@omicsonline.com

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

omics@omicsonline.com

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

materialsci@omicsonline.com

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

mathematics_physics@omicsonline.com

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

medical@omicsonline.com

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

neuro_psychology@omicsonline.com

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

pharma@omicsonline.com

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

social_politicalsci@omicsonline.com

1-702-714-7001 Extn: 9042

 
© 2008-2016 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version