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      Expression, Regulation and Function of Human Metallothioneins in Endothelial Cells


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          Metallothioneins (MTs) are small cysteine-rich proteins which are involved in e.g. metal homeostasis, metal detoxification and protection against oxidative stress. In addition, several MTs have been shown to regulate expression of proangiogenic growth factors like vascular endothelial growth factor. Detailed information about the expression and regulation of specific MT isoforms in endothelial cells (EC) is limited. We therefore performed extensive mRNA expression profiling of all known human MTs in EC. We found that the basal endothelial expression is restricted to MT1E, MT1X, MT2A, and MT3. Physiological activation of EC by exposure to serum increased the expression of MT1E and MT2A and induced the expression of MT1M. Furthermore, exposure to zinc or copper induced the expression of most MT1 isoforms, while hypoxia specifically increased the expression of MT1E, MT1M, MT1X, and MT3. Finally, knockdown of the dominant MT isoform in EC, i.e. MT2A, resulted in decreased proliferation and sprouting as well as in increased migration of human umbilical vein EC. Together, these findings provide a link between MTs and angiogenesis.

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          Most cited references 23

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          Metallothionein: the multipurpose protein

           J Philcox,  P. Coyle,  A Rofe (2002)
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            HMEC-1: Establishment of an Immortalized Human Microvascular Endothelial Cell Line

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              Targeted disruption of metallothionein I and II genes increases sensitivity to cadmium.

              We inactivated the mouse metallothionein (MT)-I and MT-II genes in embryonic stem cells and generated mice homozygous for these mutant alleles. These mice were viable and reproduced normally when reared under normal laboratory conditions. They were, however, more susceptible to hepatic poisoning by cadmium. This proves that these widely expressed MTs are not essential for development but that they do protect against cadmium toxicity. These mice provide a means for testing other proposed functions of MT in vivo.

                Author and article information

                J Vasc Res
                Journal of Vascular Research
                S. Karger AG
                August 2014
                09 August 2014
                : 51
                : 3
                : 231-238
                aAngiogenesis Laboratory, Department of Medical Oncology, bDepartment of Physiology, Institute for Cardiovascular Research, and cDepartment of Radiotherapy, VU University Medical Center, Amsterdam, The Netherlands
                Author notes
                *Dr. Victor L. Thijssen, Departments of Medical Oncology and Radiotherapy, VU University Medical Center, De Boelelaan 1118, NL-1081HV Amsterdam (The Netherlands), E-Mail v.thijssen@vumc.nl
                365550 J Vasc Res 2014;51:231-238
                © 2014 S. Karger AG, Basel

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                Page count
                Figures: 4, Tables: 2, Pages: 8
                Research Paper


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