Search

Your search keyword '"Dhayade S"' showing total 2 results
Start Over Author "Dhayade S" Journal cell reports
2 results on '"Dhayade S"'

1. Acetate Recapturing by Nuclear Acetyl-CoA Synthetase 2 Prevents Loss of Histone Acetylation during Oxygen and Serum Limitation.

Author

Bulusu V, Tumanov S, Michalopoulou E, van den Broek NJ, MacKay G, Nixon C, Dhayade S, Schug ZT, Vande Voorde J, Blyth K, Gottlieb E, Vazquez A, and Kamphorst JJ

Subjects
Acetate-CoA Ligase antagonists & inhibitors, Acetate-CoA Ligase genetics, Acetates chemistry, Acetyl Coenzyme A metabolism, Acetylation, Carbon Isotopes chemistry, Cell Line, Tumor, Cell Nucleus enzymology, Chromatography, High Pressure Liquid, Culture Media chemistry, Humans, Mass Spectrometry, Metabolome, Microscopy, Fluorescence, Mitochondria metabolism, RNA Interference, RNA, Small Interfering metabolism, Serum chemistry, Acetate-CoA Ligase metabolism, Acetates metabolism, Cell Hypoxia, Histones metabolism
Abstract

Acetyl-CoA is a key metabolic intermediate with an important role in transcriptional regulation. The nuclear-cytosolic acetyl-CoA synthetase 2 (ACSS2) was found to sustain the growth of hypoxic tumor cells. It generates acetyl-CoA from acetate, but exactly which pathways it supports is not fully understood. Here, quantitative analysis of acetate metabolism reveals that ACSS2 fulfills distinct functions depending on its cellular location. Exogenous acetate uptake is controlled by expression of both ACSS2 and the mitochondrial ACSS1, and ACSS2 supports lipogenesis. The mitochondrial and lipogenic demand for two-carbon acetyl units considerably exceeds the uptake of exogenous acetate, leaving it to only sparingly contribute to histone acetylation. Surprisingly, oxygen and serum limitation increase nuclear localization of ACSS2. We find that nuclear ACSS2 recaptures acetate released from histone deacetylation for recycling by histone acetyltransferases. Our work provides evidence for limited equilibration between nuclear and cytosolic acetyl-CoA and demonstrates that ACSS2 retains acetate to maintain histone acetylation., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2017
Full Text
View/download PDF

2. Sildenafil Potentiates a cGMP-Dependent Pathway to Promote Melanoma Growth.

Author

Dhayade S, Kaesler S, Sinnberg T, Dobrowinski H, Peters S, Naumann U, Liu H, Hunger RE, Thunemann M, Biedermann T, Schittek B, Simon HU, Feil S, and Feil R

Subjects
Animals, Butadienes pharmacology, Cell Line, Tumor, Cell Movement drug effects, Cell Proliferation drug effects, Cyclic GMP-Dependent Protein Kinase Type I chemistry, Cyclic GMP-Dependent Protein Kinase Type I genetics, Cyclic GMP-Dependent Protein Kinase Type I metabolism, Cyclic Nucleotide Phosphodiesterases, Type 5 chemistry, Cyclic Nucleotide Phosphodiesterases, Type 5 metabolism, Female, Humans, Melanoma drug therapy, Melanoma metabolism, Melanoma pathology, Mice, Mice, Inbred C57BL, Mitogen-Activated Protein Kinase 1 antagonists & inhibitors, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3 antagonists & inhibitors, Mitogen-Activated Protein Kinase 3 metabolism, Natriuretic Peptide, C-Type toxicity, Nitriles pharmacology, Phosphodiesterase 5 Inhibitors pharmacology, Protein Isoforms genetics, Protein Isoforms metabolism, Sildenafil Citrate therapeutic use, Transplantation, Homologous, Cyclic GMP metabolism, Signal Transduction drug effects, Sildenafil Citrate pharmacology
Abstract

Sildenafil, an inhibitor of the cGMP-degrading phosphodiesterase 5 that is used to treat erectile dysfunction, has been linked to an increased risk of melanoma. Here, we have examined the potential connection between cGMP-dependent signaling cascades and melanoma growth. Using a combination of biochemical assays and real-time monitoring of melanoma cells, we report a cGMP-dependent growth-promoting pathway in murine and human melanoma cells. We document that C-type natriuretic peptide (CNP), a ligand of the membrane-bound guanylate cyclase B, enhances the activity of cGMP-dependent protein kinase I (cGKI) in melanoma cells by increasing the intracellular levels of cGMP. Activation of this cGMP pathway promotes melanoma cell growth and migration in a p44/42 MAPK-dependent manner. Sildenafil treatment further increases intracellular cGMP concentrations, potentiating activation of this pathway. Collectively, our data identify this cGMP-cGKI pathway as the link between sildenafil usage and increased melanoma risk., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2016
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results