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Hyperglycemia increases prorenin receptor localization at the cell plasma membrane (1173.7)
Author(s) -
Prieto Minolfa,
Arita Danielle,
Bourgeois Camille,
Satou Ryosuke
Publication year - 2014
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.28.1_supplement.1173.7
Subject(s) - medicine , endocrinology , receptor , diabetic nephropathy , chemistry , kidney , insulin , diabetes mellitus , biology
The prorenin receptor (PRR) elicits intracellular signals linked to tissue fibrosis based upon its capability to bind prorenin at the plasma membrane (PM) which may contribute to nephropathy and microvascular changes in diabetes mellitus (DM). To test the hypothesis that hyperglycemia increases the capability of PRR to bind prorenin by increasing membrane bound PRR to PM in collecting duct cells, we used type 1 DM rats (N=10) induced with a single STZ injection (ip; 200ng/kg) as well as in M‐1 cells to assess PRR trafficking alteration induced by hyperglycemia. After 7‐days induction, STZ‐rats had levels of plasma glucose of 428±13 vs. 138±9 gr/dL and plasma insulin 0.07±0.02 vs. 2.42 ng/mL compared to control rats. By immunoflurescence (IF) studies of the rat kidney section, PRR was mainly localized predominantely on the pical aspect of collecting duct cells in STZ‐rats while in control rats most of PRR immunoreactivity was observed intracellularly. In methanol‐fixed M‐1 cells, PRR was localized mainly to the perinuclear areas in normal glucose (NG; 1g/L glucose + 1 g/L mannitol)‐treated cells. However, in high glucose (HG; 4g/L)‐treated cells, PRR was predominantly localized toward the surface, as it was appreciated in the de‐convoluted images. Although PRR mRNA levels were not different in the collecting ducts of renal medulla between groups; PRR protein levels (37 kDa) were significantly higher in PM extracts from M‐1 cells treated with HG for 5 minutes, 1, and 6 hours (with a maximum peak observed at 1 hour) than in those treated with NG. These data suggest that hyperglycemia induces PRR trafficking alterations of PRR. The effect of hyperglycemia to increase PRR abundance in PM in the collecting duct may be a novel mechanism underlying the increased hypertension seen in the diabetic patients. Grant Funding Source : Supported by NIH‐DSNTR grant