Restoration of Holoceruloplasmin Synthesis in LEC Rat after Infusion of Recombinant Adenovirus Bearing WND cDNA

• DOI: 10.1074/jbc.273.3.1815
• Publication Date: 2002-07-26T14:47:21Z
• Authors: Kunihiko Terada; Tatsushi Nakako; Xiao-Li Yang; Masatake Iida; Namiko Aiba; Yoshihiro Minamiya; Michio Nakai; Toshiyuki Sakaki; Naoyuki Miura; Toshihiro Sugiyama
• Keywords: Ceruloplasmin; Menkes disease

Wilson's disease, an autosomal recessive disorder, is characterized by the excessive accumulation of copper in liver. <i>WND</i> (<i>ATP7B</i>) gene, which encodes a putative transporting P-type ATPase, defective patients. To investigate <i>in vivo</i> function WND protein as well its intracellular localization, <i>WND</i>cDNA was introduced to Long-Evans Cinnamon rat, known rodent model for recombinant adenovirus-mediated gene delivery. An immunofluorescent study and subcellular fractionation revealed transgene expression liver localization Golgi apparatus. Moreover, since synthesis holoceruloplasmin disturbed plasma level holoceruloplasmin, oxidase-active copper-bound form, examined evaluate with respect transport. Consequently, appearance confirmed Western blot analysis measurements oxidase activity content. These findings indicate that may transport coupled ceruloplasmin apparatus likely site manifest function.