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.

Keywords::

• carbonylation
• placental membrane proteins
• insulin receptor
• insulin-like growth factor receptors
• preeclampsia
• diabetes mellitus

Acknowledgments

This work was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia, grant number: 173042.

Declaration of interest

The authors stated that there are not conflicts of interest regarding the publication of this article.