Carnosine influences transcription via epigenetic regulation as demonstrated by enhanced histone acetylation of the pyruvate dehydrogenase kinase 4 promoter in glioblastoma cells

Amino Acids
Henry OppermannFrank Gaunitz

Abstract

Carnosine (β-alanyl-L-histidine) affects a plethora of signaling pathways and genes in different biological systems. Although known as a radical scavenger, not all of these effects can simply be ascribed to its chemical nature. As previous experiments pointed towards the possibility that carnosine affects epigenetic regulation via histone acetylation, we investigated this hypothesis using the glioblastoma cell lines U87 and T98G in which carnosine's anti-neoplastic effect is accompanied by increased expression of pyruvate dehydrogenase kinase 4. Viability and expression of PDK4 was analyzed after incubation in carnosine and different histone deacetylase inhibitors (HDACi) using cell-based assays and qRT-PCR. In addition, chromatin immunoprecipitation (ChIP) experiments were performed and the global influence of carnosine on histone H3 acetylation was analyzed by Western blot. Carnosine as well as the HDACi used increased expression of PDK4. In addition, all compounds reduced cell viability, although differences were observed with regard to magnitude and required concentrations. ChIP analysis revealed increased acetylation of histone H3 in the PDK4 promoter of U87 and T98G cells (~ 1.3- and ~ 1.7-fold, respectively) 6 h after th...Continue Reading

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Citations

Mar 20, 2019·Cancer Chemotherapy and Pharmacology·Henry OppermannFrank Gaunitz
Jan 9, 2019·Amino Acids·Wim DeraveShahid P Baba
Aug 14, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·Mark D TurnerAlan R Hipkiss

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Methods Mentioned

BETA
histone acetylation
histone
immunoprecipitation
Assay
ChIP
electrophoresis
PCR
acetylation

Software Mentioned

Studio
Gene
OriginPro
Excel
Rotor
Image

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