C/EBP Homologous Protein-Mediated Endoplasmic Reticulum Stress-Related Renal Apoptosis Is Involved in Rats With Brain Death

• Transplantation has evolved from an experimental operation to a standard treatment for end-stage disease. Previous studies have demonstrated an inferior graft survival for the heart, lung, and liver from brain dead (BD) compared with living donors.
• Increased levels of apoptosis mediators in the donor are associated with a poor graft dysfunction.
• To date, there have been no studies reporting the role of kidney endoplasmic reticular stress (ERS) in organ dysfunction after BD. We have investigated the activation of ERS and apoptosis in the rat kidney after BD.

BackgroundC/EBP homologous protein (CHOP) is an important marker in endoplasmic reticulum stress (ERS)-associated cell apoptosis. The role of CHOP-induced renal apoptosis remains unclear in rats with brain death (BD). The present study aims to investigate the possible implication of CHOP-mediated, ERS-related BD-induced apoptosis in rats.Materials and MethodsForty male Sprague–Dawley rats were divided randomly into 4 experimental groups. We examined activation of ERS and apoptosis-related protein expression using Western blot and immunohistochemical staining. In addition, apoptosis is assessed by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay.ResultsKidneys harvested after BD show increased ERS- and apoptosis-related protein markers compared with kidneys of non-BD rats. Salubrinal (Sal) significantly increased levels of p-eIF2a and decreased the activity of CHOP at 6 hours after BD compared with vehicle-treated dimethylsulfoxide.ConclusionsTreating the BD donor with Sal influences renal apoptosis compared with vehicle-treated BD rats. Our results indicate that targeting the CHOP pathway provides a promising therapeutic approach for kidney injury associated with donor BD.