Trends Cell Biol. Author manuscript; available in PMC 2019 Sep 1.

Vitamin C in Stem Cell Reprogramming and Cancer

Luisa Cimmino, Ph.D.,1,2,# Benjamin G. Neel,2 and Iannis Aifantis, Ph.D.1,2,#
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1Department of Pathology, NYU School of Medicine, New York, NY, 10016, USA.
2Laura and Isaac Perlmutter Cancer Center and Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, NY, 10016, USA.

Abstract
Vitamin C is an essential dietary requirement for humans. In addition to its known role as an anti-oxidant, vitamin C is a cofactor for Fe2+ and α-ketoglutarate-dependent dioxygenases, which comprise a large number of diverse enzymes, including collagen prolyl hydroxylases and epigenetic regulators of histone and DNA methylation. Vitamin C can modulate embryonic stem cell (ESC) function, enhance reprogramming of fibroblasts to induced pluripotent stem cells (iPSCs) and hinder the aberrant self-renewal of hematopoietic stem cells (HSCs) through its ability to enhance the activity of either Jumonji-C-domain containing histone demethylases or ten-eleven translocation (TET) DNA hydroxylases. Given that epigenetic dysregulation is a known driver of malignancy, vitamin C may play a novel role as an epigenetic anti-cancer agent.

Keywords: Vitamin C, anti-oxidant, epigenetic reprogramming, stem cells, histone demethylases, TET proteins, 5-hydroxmethylcytosine, DNA methylation, leukemia, cancer therapy

Vitamin C in Stem Cell Reprogramming and Cancer
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6102081/

　

NATURE
Contribution of multidrug and toxin extrusion protein 1 (MATE1) to renal secretion of trimethylamine-N-oxide (TMAO)
A. Gessner, J. König & M. F. Fromm


Abstract
Trimethylamine-N-oxide (TMAO) gained considerable attention because of its role as a cardiovascular risk biomarker. Organic cation transporter 2 (OCT2) mediates TMAO uptake into renal proximal tubular cells. Here we investigated the potential role of multidrug and toxin extrusion protein 1 (MATE1) for translocation of TMAO across the luminal membrane of proximal tubular cells. HEK293 cells stably expressing OCT2 (HEK-OCT2) or MATE1 (HEK-MATE1) were used for uptake studies. Transcellular transport of TMAO was investigated using monolayers of MDCK control cells (MDCK-Co) as well as single- (MDCK-OCT2, MDCK-MATE1) and double-transfected cells (MDCK-OCT2-MATE1). In line with previous studies, HEK-OCT2 cells revealed a 2.4-fold uptake of TMAO compared to control cells (p < 0.001), whereas no significant uptake was observed in HEK-MATE1. In monolayers of MDCK cells, polarised TMAO transcellular transport was not significantly different between MDCK-Co and MDCK-OCT2 cells, but significantly increased in MDCK-MATE1 (p < 0.05) and MDCK-OCT2-MATE1 cells (p < 0.001). The OCT/MATE inhibitor trimethoprim abolished TMAO translocation in MDCK-OCT2-MATE1 cells (p < 0.05). The present data suggest that MATE1 contributes to renal elimination of TMAO. For selected MATE substrates, such as TMAO, uptake studies using non-polarised MATE-expressing cells can reveal false negative results compared to studies using polarised monolayers.

Contribution of multidrug and toxin extrusion protein 1 (MATE1) to renal secretion of trimethylamine-N-oxide (TMAO) | Scientific Reports
https://www.nature.com/articles/s41598-018-25139-8