title: Oxidation of placental insulin and insulin-like growth factor receptors in mothers with diabetes mellitus or preeclampsia complicated with intrauterine growth restriction.
abstract: Placental insulin receptor (IR) and insulin-like growth factor receptors (IGFRs) are essential for fetal growth. We investigated structural changes of these receptors exposed to increased oxidative stress in mothers diagnosed with diabetes mellitus (DM) or preeclampsia (PE) complicated with intrauterine growth restriction. Increased amount of IR and decreased amounts of IGF1R and IGF2R were found in both pathologies, accompanied by significant elevation in protein carbonyls. When isolated receptors were examined, increased carbonylation of IR and IGF1R in PE placentas was detected, whereas the amounts of carbonylated IR and IGF1R were similar in DM and healthy placentas. Carbonylation status of IGF2R did not change due to pathology, confirming the detrimental role of primary structure and conformation in oxidative susceptibility. Ligand binding was similar in all three groups of samples and did not seem to be affected by receptor oxidation. Since babies delivered by mothers with PE were smaller than the referent population, increased carbonylation of receptors might have affected downstream receptor signaling post-ligand binding.
authors: Department for Metabolism, INEP - Institute for the Application of Nuclear Energy, University of Belgrade , Belgrade , Republic of Serbia.
authors: D
authors: D
authors: Robajac
authors: R
authors: R
authors: Masnikosa
authors: Ž
authors: Ž
authors: Miković
authors: V
authors: V
authors: Mandić
authors: O
authors: O
authors: Nedić
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008875:Middle Aged; D010084:Oxidation-Reduction; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism*; D011485:Protein Binding; D050050:Protein Carbonylation; D017451:Receptors, Somatomedin / Q000378:metabolism*; D055815:Young Adult
chemical_list: D007328:Insulin; D017451:Receptors, Somatomedin
keywords: carbonylation; diabetes mellitus; insulin receptor; insulin-like growth factor receptors; placental membrane proteins; preeclampsia