alexa Essential Role of Phospholipase C-g1 in Hypoxia-Induced Pulmonary Vasoconstriction and Hypertension | OMICS International
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: [email protected]

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

  • 3rd International Conference on Molecular Biology & Nucleic Acids August 27-28, 2018 Toronto, Ontario, Canada.
    August 27-28, 2018 Toronto, Canada
  • 5th International Conference on Glycobiology, Lipids & Proteomics August 27-28, 2018 Toronto, Ontario, Canada.
    August 27-28, 2018 Toronto, Canada
  • International Conference on Computational Biology and Bioinformatics Sep 05-06 2018 Tokyo, Japan.
    Sep 05-06 2018 Tokyo, Japan
  • International Conference on Nutritional Biochemistry September 10-11, 2018 Prague, Czech Republic.
    September 10-11, 2018 Prague, Czech Republic
  • 4th International Conference on Enzymology and Lipid Science September 17-18, 2018 Singapore.
    September 17-18, 2018 Singapore City, Singapore
  • 4th Glycobiology World Congress September 17-19, 2018 Rome, Italy.
    September 17-19, 2018 Rome, Italy
  • 12thInternational Conference on Advancements in Bioinformatics and Drug Discovery November 26-27, 2018 Dublin, Ireland.
    November 26-27, 2018 Dublin, Ireland
  • 4th International Conference on Genetic and Protein Engineering December 05-06, 2018 Chicago, USA
    ,

Article Usage

  • Total views: 11955
  • [From(publication date):
    September-2013 - Jul 21, 2018]
  • Breakdown by view type
  • HTML page views : 8175
  • PDF downloads : 3780
 

Post your comment

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

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