Premium
Sex‐Specific Cell Death Response Following Renal Ischemia‐Reperfusion in Spontaneously Hypertensive Rats (SHR)
Author(s) -
Crislip G. Ryan,
Sullivan Jennifer C.
Publication year - 2016
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.30.1_supplement.964.9
Subject(s) - tunel assay , apoptosis , programmed cell death , necrosis , medicine , creatinine , ischemia , endocrinology , kidney , renal ischemia , andrology , cause of death , reperfusion injury , biology , immunohistochemistry , biochemistry , disease
Males develop a greater extent of ischemia‐reperfusion (IR) induced injury than females. Recent studies have shown that renal IR injury is primarily mediated by necrosis in male mice, and pilot studies in our lab indicate a sex difference in renal cell death in SHR with females having more apoptotic cell death than males under control conditions. Based on the potential protective role of apoptosis vs. necrosis, the goal of this study was to test the hypothesis that males exhibit greater necrotic cell death following IR while female SHR favor apoptotic cell death. 13 week old male and female SHR were studied: control and 45 minute warm bilateral renal ischemia followed by 24 hours reperfusion (N=6–9). Renal injury was assessed by measuring plasma creatinine (PCr) and histological analysis. Kidneys were harvested to measure cell death via TUNEL assay, PCR Arrays, and Western blot analysis. IR increased PCr in both sexes (M: 0.34±0.04 vs. 3.07±0.5; F: 0.41±0.06 vs. 2.81±0.6), although kidneys from males exhibited a greater extent of red blood cell clogging than females when stained slides were scored (M: 1.0±0.0 vs. 2.4±0.2; F: 1.1±0.1 vs. 1.8±0.3). IR increased renal apoptotic cell death in both sexes, although females tended to have greater apoptotic cell death than males (M: 1.6±0.6 vs 12.0±3.9; F: 5.0±1.0 vs 18.3±3.9 cells per area; effect of treatment: p=0.01; effect of sex: p=0.1). RIP3 activates the formation of a pro‐necrotic complex with RIP1 during the cell death process. RIP3 mRNA increased 24 hours post‐IR in both sexes, although the increase only reached significance in males (M: p=0.01; F: p=0.09; n=4). RIP1 mRNA decreased only in females (M: p=0.8; F: p=0.03; n=4), however, the protein expression decreased in both sexes (M: 0.27±0.02 vs. 0.15±0.03; F: 0.31±0.01 vs. 0.20±0.05; effect of treatment: p=0.003; effect of sex: p=0.1). These data support a sex‐specific cell death response following renal IR with greater necrotic cell death in males and greater apoptotic cell death in females. A sex difference in cell death may underlie the sex difference observed in renal IR induced injury. Support or Funding Information American Heart Association Predoctoral Fellowship; AHA Award Number: 15PRE25850008 (PI: Sullivan)