title: Cellular uptake mechanisms and responses to NO transferred from mono- and poly-S-nitrosated human serum albumin.
abstract: Endogenous S-nitrosated human serum albumin (E-Mono-SNO-HSA) is a large molecular weight nitric oxide (NO) carrier in human plasma, which has shown many beneficial effects in different animal models. To construct more efficient SNO-HSA preparations, SNO-HSA with many conjugated SNO groups has been prepared using chemical modification (CM-Poly-SNO-HSA). We have compared the properties of such a preparation to those of E-Mono-SNO-HSA. Cellular uptake of NO from E-Mono-SNO-HSA partly takes place via low molecular weight thiol, and it results in cytoprotective effects by induction of heme oxygenase-1. By contrast, transfer of NO from CM-Poly-SNO-HSA into the cells is faster and more pronounced. The influx mainly takes place by cell-surface protein disulfide isomerase. The considerable NO inflow results in apoptotic cell death by ROS induction and caspase-3 activation. Thus, increasing the number of SNO groups on HSA does not simply intensify the cellular responses to the product but can also result in very different effects.
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ishima
authors.forename: Fumika
authors.initials: F
authors.lastname: Yoshida
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kragh-Hansen
authors.forename: Kaori
authors.initials: K
authors.lastname: Watanabe
authors.forename: Naohisa
authors.initials: N
authors.lastname: Katayama
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nakajou
authors.forename: Takaaki
authors.initials: T
authors.lastname: Akaike
authors.forename: Toshiya
authors.initials: T
authors.lastname: Kai
authors.forename: Toru
authors.initials: T
authors.lastname: Maruyama
authors.forename: Masaki
authors.initials: M
authors.lastname: Otagiri
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism*; D015538:Nitrosation; D009603:Nitroso Compounds / Q000138:chemical synthesis* / Q000378:metabolism*; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D012709:Serum Albumin / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D000075462:Serum Albumin, Human
chemical_list: D009603:Nitroso Compounds; C511514:S-nitrosoalbumin, human; D012709:Serum Albumin; D009569:Nitric Oxide; D019704:Protein Disulfide-Isomerases; D003545:Cysteine; D000075462:Serum Albumin, Human