期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 452, 期 C, 页码 1-14出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2017.04.005
关键词
Hyperphosphorylation; Cellular stress-stimuli; IGF bioavailability; FGR; MRM-MS; Dual immunofluorescence immunocytochemistry
资金
- Natural Science and Engineering Council of Canada Discovery grant (NSERC) [RGPIN-2016-04752, RGPIN-2015-05000]
- Lawson Health Research Institute [HRF0512]
Phosphorylation of decidual IGFBP-1 enhances binding of IGF-I, limiting the bioavailability of this growth factor which may contribute to reduced placental and fetal growth. The mechanisms regulating decidual IGFBP-1 phosphorylation are incompletely understood. Using decidualized human immortalized endometrial stromal cells we tested the hypothesis that low oxygen tension or reduced leucine availability, believed to be common in placental insufficiency, increase the phosphorylation of decidual IGFBP-1. Multiple reaction monitoring-MS (MRM-MS) was used to quantify IGFBP-1 phosphorylation. MRM-MS validated the novel phosphorylation of IGFBP-1 at Ser58, however this site was unaffected by low oxygen tension/leucine deprivation. In contrast, significantly elevated phosphorylation was detected for pSer119, pSer98/pSer101 and pSer169/pSer174 sites. Immunoblotting and dual-immunofluorescence using phosphosite-specific IGFBP-1 antibodies further demonstrated increased IGFBP-1 phosphorylation in HIESC under both treatments which concomitantly reduced IGF-I bioactivity. These data support the hypothesis that down regulation of IGF-I signaling links decidual IGFBP-1 hyperphosphorylation to restricted fetal growth in placental insufficiency. (C) 2017 Published by Elsevier Ireland Ltd.
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