TY - JOUR
T1 - Cellular uptake mechanisms and responses to NO transferred from mono-and poly-S-nitrosated human serum albumin
AU - Ishima, Yu
AU - Yoshida, Fumika
AU - Kragh-Hansen, Ulrich
AU - Watanabe, Kaori
AU - Katayama, Naohisa
AU - Nakajou, Keisuke
AU - Akaike, Takaaki
AU - Kai, Toshiya
AU - Maruyama, Toru
AU - Otagiri, Masaki
N1 - Funding Information:
Declaration of interest: The authors declare that they have no conflict of interest. This research was supported [in part] by Grant-in-Aid for Scientific Research from Japan Society for the Promotion of Science (JSPS) (KAKENHI 18390051 and 22790162).This work was in part supported by grants from the Uehara Memorial Fund.
PY - 2011/10
Y1 - 2011/10
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Cell-surface protein disulfide isomerase
KW - Cytoprotection
KW - Nitric oxide
KW - S-nitrosation
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U2 - 10.3109/10715762.2011.606814
DO - 10.3109/10715762.2011.606814
M3 - Article
C2 - 21781009
AN - SCOPUS:80052706434
SN - 1071-5762
VL - 45
SP - 1196
EP - 1206
JO - Free Radical Research
JF - Free Radical Research
IS - 10
ER -