Premium
Differential Expression g‐H2AX and RAGE in the Placenta of Gestational Diabetes Mellitus (GDM), Preterm Labor (PTL) and Preeclampsia Patients
Author(s) -
Tsai K YF,
Hirschi K M,
Davis T,
Llavina S,
Knowlton M N,
Bennet A,
Reynolds P R,
Arroyo J A
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.496.24
Subject(s) - placenta , dna damage , rage (emotion) , glycation , preeclampsia , biology , dna repair , dna , cancer research , medicine , endocrinology , andrology , diabetes mellitus , pregnancy , fetus , genetics , neuroscience
The integrity of the genome is fundamental for human health. Defective DNA repair response (DRR) is associated with several diseases, including pulmonary fibrosis, neurodegeneration, and in diseased placenta. The most destructive form of genomic damage is known to be DNA double strand breaks (DNA‐DSBs), in which both strands of DNA are ruptured. g‐H2AX is a component of the histone octomer and is phosphorylated in response to DNA‐DSBs. The receptor for advanced glycation end‐products (RAGE) is a multi‐ligand receptor primarily expressed on cell membranes, where it functions as a progression factor in inflammatory signaling; however, the nuclear isoform of RAGE (nRAGE) has been described as having a crucial role in DNA‐DSBs repair. The purpose of this study was to identify placental nRAGE and g‐H2AXexpression during normal gestation (Control), gestational diabetes mellitus (GDM), intrauterine growth restriction (IUGR), preterm delivery (PTL) and preeclampsia (PE). Immunohistochemistry was used to determine localization of both molecules present in human placenta. Immunoblot was further used to quantify nRAGE andg‐H2AX production. Assessing DNA degradation was used to confirm placental DNA damage during pregnancy complications. Relative to controls we observed: 1) Increased staining for of RAGE and g‐H2AX in PTL and PE placentas; 2) increased placental nRAGE protein in the PTL and PE placentas; 3) increased placental g‐H2AX protein in both PTL and PE conditions; and 4) increased DNA damage in the diseased placenta. These research suggest a potential role for nRAGE during DNA‐DSB detection and repair in human PTL and PE placentas. These results may provide insight into the physiological relevance of these molecules, and if so, their modification during gestation may help alleviate placental disease. Support or Funding Information This work was supported by a grant from the Flight Attendant's Medical Research Institute (FAMRI, PRR and JAA) and a BYU Mentoring Environment Grant (JAA and PRR). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .