title: Characterization of NO-Induced Nitrosative Status in Human Placenta from Pregnant Women with Gestational Diabetes Mellitus.
abstract: Dysregulation of NO production is implicated in pregnancy-related diseases, including gestational diabetes mellitus (GDM). The role of NO and its placental targets in GDM pregnancies has yet to be determined. S-Nitrosylation is the NO-derived posttranslational protein modification that can modulate biological functions by forming NO-derived complexes with longer half-life, termed S-nitrosothiol (SNO). Our aim was to examine the presence of endogenous S-nitrosylated proteins in cysteine residues in relation to antioxidant defense, apoptosis, and cellular signal transduction in placental tissue from control (n= 8) and GDM (n= 8) pregnancies. S-Nitrosylation was measured using the biotin-switch assay, while the expression and protein activity were assessed by immunoblotting and colorimetric methods, respectively. Results indicated that catalase and peroxiredoxin nitrosylation levels were greater in GDM placentas, and that was accompanied by reduced catalase activity. S-Nitrosylation of ERK1/2 and AKT was increased in GDM placentas, and their activities were inhibited. Activities of caspase-3 and caspase-9 were increased, with the latter also showing diminished nitrosylation levels. These findings suggest that S-nitrosylation is a little-known, but critical, mechanism by which NO directly modulates key placental proteins in women with GDM and, as a consequence, maternal and fetal anomalies during pregnancy can occur.
authors.affiliation: Research Unit, Puerta del Mar University Hospital, Cádiz, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Visiedo
authors.affiliation: Research Unit, Puerta del Mar University Hospital, Cádiz, Spain.
authors.forename: Celeste
authors.initials: C
authors.lastname: Santos-Rosendo
authors.affiliation: Research Unit, Puerta del Mar University Hospital, Cádiz, Spain.
authors.forename: Rosa M
authors.identifier: 0000-0002-9853-1103
authors.initials: RM
authors.lastname: Mateos-Bernal
authors.affiliation: Department of Genetic, Faculty of Biology, University of Seville, Seville, Spain.
authors.forename: M Del Mar
authors.initials: MD
authors.lastname: Gil-Sánchez
authors.affiliation: Department of Obstetrics and Gynecology, Puerta del Mar University Hospital, Cádiz, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Bugatto
authors.affiliation: Department of Endocrinology and Nutrition, Puerta del Mar University Hospital, Cádiz, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Aguilar-Diosdado
authors.affiliation: Salus Infirmorum, Faculty of Nursing, University of Cádiz, Cádiz, Spain.
authors.forename: Carmen
authors.identifier: 0000-0003-2884-0557
authors.initials: C
authors.lastname: Segundo
authors.affiliation: Department of Obstetrics and Gynecology, Puerta del Mar University Hospital, Cádiz, Spain.
authors.forename: Cristina
authors.identifier: 0000-0002-3155-1361
authors.initials: C
authors.lastname: López-Tinoco
mesh_terms: D000328:Adult; D017209:Apoptosis; D015992:Body Mass Index; D016022:Case-Control Studies; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002585:Cesarean Section; D016640:Diabetes, Gestational / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009566:Nitrates / Q000737:chemistry* / Q000378:metabolism; D009569:Nitric Oxide / Q000737:chemistry*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D015538:Nitrosation; D054464:Peroxiredoxins / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D026403:S-Nitrosothiols / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism
chemical_list: D009566:Nitrates; D026403:S-Nitrosothiols; D009569:Nitric Oxide; D054464:Peroxiredoxins; D002374:Catalase; D052247:Nitric Oxide Synthase Type II; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053148:Caspase 3; D053453:Caspase 9