Deletion of GIT1 Impacts eNOS Activity To Aggravate sFlt-1–Induced Preeclampsia Phenotype in Mice

G3: Genes, Genomes, Genetics

article

Shenghong Zhang¹  Cuili Zou¹  Qiaoqin Zhang¹ 

[1] Heze Municipal Hospital, Heze City 274000, Shandong Province, China

关键词: preeclampsia;    endothelial nitric oxide synthases (eNOS);    G-protein-coupled Receptor Kinase Interactor-1 (GIT1);    NO production;    urinary albumin excretion (UAE);    blood pressure (BP);   

DOI  :  10.1534/g3.118.200509

学科分类：社会科学、人文和艺术（综合）

来源: Genetics Society of America

【 摘 要 】

Preeclampsia, a serious multisystem disorder specific to human pregnancy, remains a considerable burden of disease worldwide. Reduced nitric oxide bioavailability is proved to be crucial in the maternal and fetal pathophysiology of preeclampsia. G-protein-coupled Receptor Kinase Interactor-1 (GIT1) is a novel endothelial nitric oxide synthases (eNOS) interactor mediator. The aim of this paper is to investigate the effect of GIT1 on preeclampsia. Blood pressure (BP) was measured using a carotid catheter-calibrated eight-chamber tail-cuff system (CODA) at the same time daily. Urinary albumin excretion (UAE) was determined using Albuwell-M kits (Exocell Inc) and creatinine clearance (CCr) was determined by measuring urinary creatinine concentration with tandem liquid chromatography–mass spectrometry. The release of nitrite was analyzed to detect nitric oxide (NO) production using a Sievers Chemiluminescence NO Analyzer. NOS activity was examined by measuring the conversion of ³H-labeled l -arginine to ³H-labeled l -citrulline. BP was significantly increased in GIT1^−/− mice with or without sFIT-1 treatment. In addition, GIT1−/− mice possessed higher UAE and lower CCr. Depletion of GIT1 impedes the NO production and placenta eNOS activity. Additional GIT1 attenuates sFlt-1-induced preeclampsia phenotypes. Our findings suggest that GIT1 significantly extenuates the sFlt-1-induced preeclampsia phenotypes by inhibiting eNOS activity, indicating a crucial role of GIT1 in the progression of preeclampsia.

【 授权许可】

CC BY|CC BY-NC