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Copper Accumulates in Hemosiderins in Livers of Patients with Iron Overload Syndromes

Journal of Clinical and Translational Hepatology 2015年第2期3卷 85-92页

作者： Yukiya Ono Masatoshi Ishigami Kazuhiko Hayashi Shinya Wakusawa Hisao Hayashi Kotaro Kumagai Natsuko Morotomi Tetsuji Yamashita Miwa Kawanaka minemori watanabe Hiroaki Ozawa Mayumi Tai Hiroaki Miyajima Kentarou Yoshioka Yoshiki Hirooka Hidemi Goto Department of Gastroenterology Nagoya University Graduate School of Medicine Nagoya Japan Department of Medical Laboratory Sciences Nagoya University Graduate School of Medicine Nagoya Japan Department of Medicine Aichi Gakuin University School of Pharmacy Nagoya Japan Digestive Disease and Lifestyle Related Disease Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan Department of Internal Medicine Moji Hospital Kitakyushu Japan Department of Medicine Yoshida Hospital Matsuyama Japan General Internal Medicine 2 Kawasaki Hospital Kawasaki Medical School Okayama Japan Department of Endocrinology and Diabetes Okazaki City Hospital Okazaki Japan Department of Pathology Okazaki City Hospital Okazaki Japan Department of Gastroenterology Fukushima Rohsai Hospital Fukushima Japan First Department of Medicine Hamamatsu University School of Medicine Hamamatsu Japan Department of Liver Biliary Tract and Pancreas Diseases Fujita Health University Toyoake Japan

In biology,redox reactions are essential and sometimes harmful,and therefore,iron metabolism is tightly regulated by cuproproteins.Since the state of copper in iron overload syndromes remains unclear,we investigated whether copper metabolism is altered in these syndromes.Eleven patients with iron overload syndromes participated in this study.The clinical diagnoses were aceruloplasminemia (n=2),hemochromatosis (n=5),ferroportin disease (n=2),and receiving excess intravenous iron supplementation (n=2).Liver specimens were analyzed using a light microscope and transmission electron microscope equipped with an X-ray analyzer.In addition to a large amount of iron associated with oxygen and phosphorus,the iron-rich hemosiderins of hepatocytes and Kupffer cells contained small amounts of copper and sulfur,regardless of disease etiology.Two-dimensional imaging clearly showed that cuproproteins were distributed homogenously with iron complexes within hemosiderins.Copper stasis was unlikely in noncirrhotic patients.The enhanced induction of cuproproteins by excess iron may contribute to copper accumulation in hemosiderins.In conclusion,we have demonstrated that copper accumulates in hemosiderins in iron overload conditions,perhaps due to alterations in copper metabolism.

关键词： Aceruloplasminemia Cuproprotein induction Ferroportin disease Hemochromatosis Hemosiderin Iron copper interaction Iron overload syndromes

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