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Translational Medical Research Commons™

Open Access. Powered by Scholars. Published by Universities.®

Medical Biochemistry

Thomas Jefferson University

Series

Articles 1 - 4 of 4

Full-Text Articles in Translational Medical Research

The Histone Deacetylase Inhibitor Tubacin Mitigates Endothelial Dysfunction By Up-Regulating The Expression Of Endothelial Nitric Oxide Synthase., Jihui Chen, Jian Zhang, Noor F. Shaik, Bing Yi, Xin Wei, Xiao-Feng Yang, Ulhas P. Naik, Ross Summer, Guijun Yan, Xinyun Xu, Jianxin Sun Dec 2019

The Histone Deacetylase Inhibitor Tubacin Mitigates Endothelial Dysfunction By Up-Regulating The Expression Of Endothelial Nitric Oxide Synthase., Jihui Chen, Jian Zhang, Noor F. Shaik, Bing Yi, Xin Wei, Xiao-Feng Yang, Ulhas P. Naik, Ross Summer, Guijun Yan, Xinyun Xu, Jianxin Sun

Center for Translational Medicine Faculty Papers

Endothelial nitric oxide (NO) synthase (eNOS) plays a critical role in the maintenance of blood vessel homeostasis. Recent findings suggest that cytoskeletal dynamics play an essential role in regulating eNOS expression and activation. Here, we sought to test whether modulation of cytoskeletal dynamics through pharmacological regulation of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation affects eNOS expression and endothelial function in vitro and in vivo.Wefound that tubulin acetylation inducer (tubacin), a compound that appears to selectively inhibit HDAC6 activity, dramatically increased eNOS expression in several different endothelial cell lines, as determined by both immunoblotting and NO production assays. Mechanistically, we found …

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The Anti-Cancer Effect Of Retinoic Acid Signaling In Crc Occurs Via Decreased Growth Of Aldh+ Colon Cancer Stem Cells And Increased Differentiation Of Stem Cells, Shirin R. Modarai, Anindita Gupta, Lynn M. Opdenaker, Ryan Kowash, Gabriel Masters, Vignesh Viswanathan, Tao Zhang, Jeremy Z. Fields, Bruce M. Boman Oct 2018

The Anti-Cancer Effect Of Retinoic Acid Signaling In Crc Occurs Via Decreased Growth Of Aldh+ Colon Cancer Stem Cells And Increased Differentiation Of Stem Cells, Shirin R. Modarai, Anindita Gupta, Lynn M. Opdenaker, Ryan Kowash, Gabriel Masters, Vignesh Viswanathan, Tao Zhang, Jeremy Z. Fields, Bruce M. Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Background: Tumorigenesis is driven by stem cell (SC) overpopulation. BecauseALDH is both a marker for SCs in many tissues and a key enzyme in retinoid acid (RA)signaling, we studied RA signaling in normal and malignant colonic SCs.Hypothesis: RA signaling regulates growth and differentiation of ALDH+ colonicSCs dysregulation of RA signaling contributes to SC overpopulation and colorectalcancer (CRC) development.Methods: We analyzed normal and malignant colonic tissues and CRC cell linesto see if retinoid receptors (RXR &RAR) are exclusively expressed in ALDH+ SCs,and if RA signaling changes during CRC development. We determined whether RAsignaling regulates cancer SC (CSC) proliferation, differentiation, sphere formation,and …

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Pepducin-Mediated Cardioprotection Via Β-Arrestin-Biased Β2-Adrenergic Receptor-Specific Signaling, Laurel A. Grisanti, Toby P. Thomas, Rhonda L. Carter, Claudio De Lucia, Erhe Gao, Walter J. Koch, Jeffrey L. Benovic, Douglas G. Tilley Sep 2018

Pepducin-Mediated Cardioprotection Via Β-Arrestin-Biased Β2-Adrenergic Receptor-Specific Signaling, Laurel A. Grisanti, Toby P. Thomas, Rhonda L. Carter, Claudio De Lucia, Erhe Gao, Walter J. Koch, Jeffrey L. Benovic, Douglas G. Tilley

Department of Biochemistry and Molecular Biology Faculty Papers

Reperfusion as a therapeutic intervention for acute myocardial infarction-induced cardiac injury itself induces further cardiomyocyte death. β-arrestin (βarr)-biased β-adrenergic receptor (βAR) activation promotes survival signaling responses in vitro; thus, we hypothesize that this pathway can mitigate cardiomyocyte death at the time of reperfusion to better preserve function. However, a lack of efficacious βarr-biased orthosteric small molecules has prevented investigation into whether this pathway relays protection against ischemic injury in vivo. We recently demonstrated that the pepducin ICL1-9, a small lipidated peptide fragment designed from the first intracellular loop of β2AR, allosterically engaged pro-survival signaling cascades in a βarr-dependent manner in …

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Coupling Of Smoothened To Inhibitory G Proteins Reduces Voltage-Gated K, Lan Cheng, Moza Al-Owais, Manuel Covarrubias, Walter J. Koch, David R. Manning, Chris Peers, Natalia A Riobo-Del Galdo Jul 2018

Coupling Of Smoothened To Inhibitory G Proteins Reduces Voltage-Gated K, Lan Cheng, Moza Al-Owais, Manuel Covarrubias, Walter J. Koch, David R. Manning, Chris Peers, Natalia A Riobo-Del Galdo

Department of Biochemistry and Molecular Biology Faculty Papers

SMO (Smoothened), the central transducer of Hedgehog signaling, is coupled to heterotrimeric Gi proteins in many cell types, including cardiomyocytes. In this study, we report that activation of SMO with SHH (Sonic Hedgehog) or a small agonist, purmorphamine, rapidly causes a prolongation of the action potential duration that is sensitive to a SMO inhibitor. In contrast, neither of the SMO agonists prolonged the action potential in cardiomyocytes from transgenic GiCT/TTA mice, in which Gi signaling is impaired, suggesting that the effect of SMO is mediated by Gi proteins. Investigation of the mechanism underlying the change …

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