title: Sex differences in shotgun proteome analyses for chronic oral intake of cadmium in mice.
abstract: Environmental diseases related to cadmium exposure primarily develop owing to industrial wastewater pollution and/or contaminated food. In regions with high cadmium exposure in Japan, cadmium accumulation occurs primarily in the kidneys of individuals who are exposed to the metal. In contrast, in the itai-itai disease outbreak that occurred in the Jinzu River basin in Toyama Prefecture in Japan, cadmium primarily accumulated in the liver. On the other hand, high concentration of cadmium caused renal tubular disorder and osteomalacia (multiple bone fracture), probably resulting from the renal tubular dysfunction and additional pathology. In this study, we aimed to establish a mouse model of chronic cadmium intake. We administered cadmium-containing drinking water (32 mg/l) to female and male mice ad libitum for 11 weeks. Metal analysis using inductively coupled plasma mass spectrometry revealed that cadmium accumulated in the kidneys (927 x 10 + 185 ng/g in females and 661 x 10 + 101 ng/g in males), liver (397 x 10 + 199 ng/g in females and 238 x 10 + 652 ng/g in males), and thyroid gland (293 + 93.7 ng/g in females and 129 + 72.7 ng/g in males) of mice. Female mice showed higher cadmium accumulation in the kidney, liver, and thyroid gland than males did (p = 0.00345, p = 0.00213, and p = 0.0331, respectively). Shotgun proteome analyses after chronic oral administration of cadmium revealed that protein levels of glutathione S-transferase Mu2, Mu4, and Mu7 decreased in the liver, and those of A1 and A2 decreased in the kidneys in both female and male mice.
authors: Isotope Research Center, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
authors: Yoshiharu
authors: Y
authors: Yamanobe
authors: Isotope Research Center, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
authors: Noriyuki
authors: N
authors: Nagahara
authors: Department of Epidemiology and Environmental Health, Juntendo University, Faculty of Medicine, Bunkyo-ku, Tokyo, Japan.
authors: Takehisa
authors: T
authors: Matsukawa
authors: Department of Pathology and Experimental Medicine, Kumamoto University Graduate School of Medical Sciences, Hongo, Kumamoto, Japan.
authors: Takaaki
authors: T
authors: Ito
authors: Department of Pathology and Experimental Medicine, Kumamoto University Graduate School of Medical Sciences, Hongo, Kumamoto, Japan.
authors: Kanako
authors: K
authors: Niimori-Kita
authors: Department of Epidemiology and Environmental Health, Juntendo University, Faculty of Medicine, Bunkyo-ku, Tokyo, Japan.
authors: Momoko
authors: M
authors: Chiba
authors: Department of Epidemiology and Environmental Health, Juntendo University, Faculty of Medicine, Bunkyo-ku, Tokyo, Japan.
authors: Kazuhito
authors: K
authors: Yokoyama
authors: Isotope Research Center, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
authors: Toshihiro
authors: T
authors: Takizawa
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002104:Cadmium / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D012727:Sex Characteristics; D015854:Up-Regulation
chemical_list: D020543:Proteome; D002104:Cadmium