Benzo[a]pyrene-induced metabolic shift from glycolysis to pentose phosphate pathway in the human bladder cancer cell line RT4

Verma N, Pink M, Boland S, Rettenmeier AW, Schmitz-Spanke S (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 7

Pages Range: 9773

Journal Issue: 1

DOI: 10.1038/s41598-017-09936-1

Abstract

Benzo[a]pyrene (B[a]P), a well-known polyaromatic hydrocarbon, is known for its lung carcinogenicity, however, its role in bladder cancer development is still discussed. Comparative two-dimensional blue native SDS-PAGE analysis of protein complexes isolated from subcellular fractions of 0.5 µM B[a]P-exposed cells indicated a differential regulation of proteins involved in carbohydrate, fatty acid, and nucleotide metabolism, suggesting a possible metabolic flux redistribution. It appeared that B[a]P exposure led to a repression of enzymes (fructose-bisphosphate aldolase A, glucose-6-phosphate isomerase, lactate dehydrogenase) involved in glycolysis, and an up-regulation of proteins (glucose-6-phosphate 1-dehydrogenase, 6-phosphogluconolactonase) catalyzing the pentose phosphate pathway and one carbon metabolism (10-formyltetrahydrofolate dehydrogenase, bifunctional purine biosynthesis protein). Untargeted metabolomics further supported the proteomic data, a lower concentration of glycolytic metabolite was observed as compared to glutamine, xylulose and fatty acids. The analysis of the glutathione and NADPH/NADP+ content of the cells revealed a significant increase of these cofactors. Concomitantly, we did not observe any detectable increase in the production of ROS. With the present work, we shed light on an early phase of the metabolic stress response in which the urothelial cells are capable of counteracting oxidative stress by redirecting the metabolic flux from glycolysis to pentose phosphate pathway.

Authors with CRIS profile

Nisha Verma Professur für Biomarker in der Arbeitsmedizin Mario Pink Lehrstuhl für Arbeits-, Sozial- und Umweltmedizin Simone Schmitz-Spanke Professur für Biomarker in der Arbeitsmedizin

Additional Organisation(s)

Exzellenz-Cluster Engineering of Advanced Materials

Involved external institutions

Universitätsklinikum Essen DE Germany (DE)

How to cite

APA:

Verma, N., Pink, M., Boland, S., Rettenmeier, A.W., & Schmitz-Spanke, S. (2017). Benzo[a]pyrene-induced metabolic shift from glycolysis to pentose phosphate pathway in the human bladder cancer cell line RT4. Scientific Reports, 7(1), 9773. https://dx.doi.org/10.1038/s41598-017-09936-1

MLA:

Verma, Nisha, et al. "Benzo[a]pyrene-induced metabolic shift from glycolysis to pentose phosphate pathway in the human bladder cancer cell line RT4." Scientific Reports 7.1 (2017): 9773.

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