title: Copper Accumulates in Hemosiderins in Livers of Patients with Iron Overload Syndromes.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yukiya
authors.initials: Y
authors.lastname: Ono
authors.affiliation: Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Ishigami
authors.affiliation: Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Department of Medical Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Wakusawa
authors.affiliation: Department of Medicine, Aichi Gakuin University School of Pharmacy, Nagoya, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Digestive Disease and Lifestyle Related Disease, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Kumagai
authors.affiliation: Department of Internal Medicine, Moji Hospital, Kitakyushu, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Morotomi
authors.affiliation: Department of Medicine, Yoshida Hospital, Matsuyama, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.
authors.forename: Miwa
authors.initials: M
authors.lastname: Kawanaka
authors.affiliation: Department of Endocrinology and Diabetes, Okazaki City Hospital, Okazaki, Japan.
authors.forename: Minemori
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Pathology, Okazaki City Hospital, Okazaki, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ozawa
authors.affiliation: Department of Gastroenterology, Fukushima Rohsai Hospital, Fukushima, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tai
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miyajima
authors.affiliation: Department of Liver, Biliary Tract and Pancreas Diseases, Fujita Health University, Toyoake, Japan.
authors.forename: Kentarou
authors.initials: K
authors.lastname: Yoshioka
authors.affiliation: Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Hirooka
authors.affiliation: Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
keywords: Aceruloplasminemia; Cuproprotein induction; Ferroportin disease; Hemochromatosis; Hemosiderin; Iron copper interaction; Iron overload syndromes