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Int. J. Mol. Sci. 2017, 18(5), 918; doi:10.3390/ijms18050918

Role of the Vanins–Myeloperoxidase Axis in Colorectal Carcinogenesis

Department of Diagnostic and Clinical Medicine, and Public Health, University of Modena and Reggio Emilia, Via Del Pozzo 71, I-41125 Modena, Italy
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Academic Editors: Takuji Tanaka and Masahito Shimizu
Received: 29 March 2017 / Revised: 20 April 2017 / Accepted: 21 April 2017 / Published: 27 April 2017
(This article belongs to the Special Issue Inflammation and Cancer)
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Abstract

The presence of chronic inflammation in the colonic mucosa leads to an increased risk of cancer. Among proteins involved in the regulation of mucosal inflammation and that may contribute both to structural damage of the intestinal mucosa and to intestinal carcinogenesis, there are myeloperoxidase (MPO) and vanins. The infiltration of colonic mucosa by neutrophils may promote carcinogenesis through MPO, a key enzyme contained in the lysosomes of neutrophils that regulates local inflammation and the generation of reactive oxygen species (ROS) and mutagenic species. The human vanin gene family consists of three genes: vanin-1, vanin-2 and vanin-3. All vanin molecules are pantetheinases, that hydrolyze pantetheine into pantothenic acid (vitamin B5), and cysteamine, a sulfhydryl compound. Vanin-1 loss confers an increased resistance to stress and acute intestinal inflammation, while vanin-2 regulates adhesion and transmigration of activated neutrophils. The metabolic product of these enzymes has a prominent role in the inflammation processes by affecting glutathione levels, inducing ulcers through a reduction in mucosal blood flow and oxygenation, decreasing local defense mechanisms, and in carcinogenesis by damaging DNA and regulating pathways involved in cell apoptosis, metabolism and growth, as Nrf2 and HIF-1α. View Full-Text
Keywords: vanins; myeloperoxidase; colorectal carcinogenesis; inflammation vanins; myeloperoxidase; colorectal carcinogenesis; inflammation
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Mariani, F.; Roncucci, L. Role of the Vanins–Myeloperoxidase Axis in Colorectal Carcinogenesis. Int. J. Mol. Sci. 2017, 18, 918.

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