The activity of proapoptotic genes increases after renal ischemia/reperfusion

Abstract

According to the World Health Organization, pathologies associated with ischemia/reperfusion occupy the leading position in the structure of mortality. The efficiency of localized kidney cancer surgery is limited by the damaging effects of prolonged warm ischemia and reperfusion. Ischemia/reperfusion damage to renal tissue may be related to changes in the expression profiles of pro- and antiapoptotic genes. Here, we have presented the longitudinal expression profiles of apoptosis-related genes in tissues of left and right (intact) kidneys of male rats exposed to unilateral ischemia followed by reperfusion. The profiles have been assessed at time points of 1, 3, and 48 h after the ischemic/reperfusion exposure by RT-qPCR quantification of mRNAs encoded by 13 genes, including BAX, p53, AIFM1, APAF1, CASP8, CASP3, CASP9, CASP7, MDM2, BCL2, CIAP1, XIAP, and ICAD, after normalization with respect to a reference gene ACTB. The study revealed a shift in the expression of pro- and antiapoptotic genes toward the predominance of proapoptotic processes, as was evinced by the increase in expression detected for the BAX, p53, AIFM1, APAF1, and CASP8 genes. One hour after the reperfusion, activation of mitochondrial, or intrinsic apoptosis was detected, while р53-dependent and extrinsic, i.e., receptor-driven, apoptosis joined at later time points. Changes in the level of expression of caspase 7 (CASP7)-encoding mRNA have only been detected 48 h after the restoration of blood flow. Changes have been observed in the transcription of pro- and antiapoptotic genes in tissues of both kidneys, which suggests the involvement of the contralateral kidney in systemic pathological process that develops during unilateral ischemia/reperfusion.