Abstract

Dr. Manganiello died in January 2016. The completion of the studies in his laboratory and publication of the results were performed by his long-time colleague Joel Moss. The areas of investigation focused on the roles of PDE3A and PDE3B in regulation of inflammation, myocardial function, and oxidative stress. A goal for FY16 was to prepare Dr. Manganiello's data for publication, and distribute his laboratory's research tools (e.g., PDE3A,B knockout mice, antibodies, cDNA) to his intramural and extramural colleagues. The studies completed or scheduled for completion included first, the role of phosphodiesterase 3B (PDE3B) in the regulation of the NLRP3 inflammasome and metabolic cross talk in adipose tissue. The second area of investigation included regulation of sarcoplasmic reticulum Ca2+ ATPase 2 (SERCA2) activity by phosphodiesterase 3A (PDE3A) in human myocardium. The third area of investigation included effects of heterologous expression of human Cyclic Nucleotide Phosphodiesterase 3A (hPDE3A) on redox regulation in yeast. Fourth, the data on phosphodiesterase 3 equivalent in C. elegans were prepared and submitted for publication.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAHL002540-22
Application #
9353094
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
22
Fiscal Year
2016
Total Cost
Indirect Cost

  Institution

Name
U.S. National Heart Lung and Blood Inst
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Zhang, Li; Pacheco-Rodriguez, Gustavo; Steagall, Wendy K et al. (2015) Tuberous sclerosis complex 2 loss of heterozygosity in patients with lung disease and cancer. Am J Respir Crit Care Med 191:352-5
Barochia, Amisha V; Kaler, Maryann; Cuento, Rosemarie A et al. (2015) Serum apolipoprotein A-I and large high-density lipoprotein particles are positively correlated with FEV1 in atopic asthma. Am J Respir Crit Care Med 191:990-1000
DiPilato, Lisa M; Ahmad, Faiyaz; Harms, Matthew et al. (2015) The Role of PDE3B Phosphorylation in the Inhibition of Lipolysis by Insulin. Mol Cell Biol 35:2752-60
Ahmad, F; Murata, T; Shimizu, K et al. (2015) Cyclic nucleotide phosphodiesterases: important signaling modulators and therapeutic targets. Oral Dis 21:e25-50
Chung, Youn Wook; Lagranha, Claudia; Chen, Yong et al. (2015) Targeted disruption of PDE3B, but not PDE3A, protects murine heart from ischemia/reperfusion injury. Proc Natl Acad Sci U S A 112:E2253-62
Ahmad, Faiyaz; Shen, Weixing; Vandeput, Fabrice et al. (2015) Regulation of sarcoplasmic reticulum Ca2+ ATPase 2 (SERCA2) activity by phosphodiesterase 3A (PDE3A) in human myocardium: phosphorylation-dependent interaction of PDE3A1 with SERCA2. J Biol Chem 290:6763-76
Andrade, Bruno B; Pavan Kumar, Nathella; Amaral, Eduardo P et al. (2015) Heme Oxygenase-1 Regulation of Matrix Metalloproteinase-1 Expression Underlies Distinct Disease Profiles in Tuberculosis. J Immunol 195:2763-73
Ke, Bilun; Zhao, Zhiyun; Ye, Xin et al. (2015) Inactivation of NF-?B p65 (RelA) in Liver Improves Insulin Sensitivity and Inhibits cAMP/PKA Pathway. Diabetes 64:3355-62
Azevedo, Monalisa F; Faucz, Fabio R; Bimpaki, Eirini et al. (2014) Clinical and molecular genetics of the phosphodiesterases (PDEs). Endocr Rev 35:195-233
Hiramoto, Kenichi; Murata, Taku; Shimizu, Kasumi et al. (2014) Role of phosphodiesterase 2 in growth and invasion of human malignant melanoma cells. Cell Signal 26:1807-17

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