NDLI: The antineoplastic effect of carnosine is accompanied by induction of PDK4 and can be mimicked by l-histidine

Content Provider	Springer Nature Link
Author	Letzien, Ulrike Oppermann, Henry Meixensberger, Jürgen Gaunitz, Frank
Copyright Year	2014
Abstract	Carnosine (β-alanyl-l-histidine) is a naturally occurring dipeptide that shows antineoplastic effects in cell culture as well as in animal experiments. Since its mode of action and the targets at the molecular level have not yet been elucidated, we performed qRT-PCR experiments with RNA isolated from glioblastoma cell lines treated with carnosine, β-alanine, l-alanine, l-histidine and the dipeptide l-alanine-l-histidine. The experiments identified a strong induction of expression of the gene encoding pyruvate dehydrogenase 4 (PDK4) under the influence of carnosine and l-histidine, but not by the other substances employed. In addition, inhibition of cell viability was only detected in cells treated with carnosine and l-histidine, with the latter showing a significantly stronger effect than carnosine. Since the tumor cells expressed the tissue form of carnosinase (CN2) but almost no serum carnosinase (CN1), we conclude that cleavage by CN2 is a prerequisite for the antineoplastic effect of carnosine. In addition, enhanced expression of PDK4 under the influence of carnosine/l-histidine opens a new perspective for the interpretation of the ergogenic potential of dietary β-alanine supplementation and adds a new contribution to a growing body of evidence that single amino acids can regulate key metabolic pathways important in health and disease.
Starting Page	1009
Ending Page	1019
Page Count	11
File Format	PDF
ISSN	09394451
Journal	Amino Acids
Volume Number	46
Issue Number	4
e-ISSN	14382199
Language	English
Publisher	Springer Vienna
Publisher Date	2014-01-08
Publisher Place	Vienna
Access Restriction	Subscribed
Subject Keyword	Carnosine l-Histidine PDK4 Glioblastoma Cancer Biochemistry Analytical Chemistry Biochemical Engineering Life Sciences Proteomics Neurobiology
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Biochemistry Clinical Biochemistry

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