Apoptosis and Autophagy in Cold Preservation Ischemia

Abstract

In summary, we have shown that autophagy and autophagic flux are reduced in cold ischemic kidneys treated with bafilomycin A1. Reduced autophagy and autophagic flux were associated with a significant reduction in apoptotic cell death, which may provide a therapeutic rationale for including bafilomycin A1 in University of Wisconsin solution during organ preservation.

Emerging role of autophagy in kidney function, diseases and aging

“…208 In rat kidneys, cold preservation using University of Wisconsin (UW) solution (a solution that is widely used for kidney preservation) increases autophagic flux and apoptotic cell death. 209 Inhibiting autophagic flux by adding bafilomycin A 1 to the UW solution reduces autophagic flux and apoptosis (and unexpectedly decreases LC3-II formation). Although the consequences of adding bafilomycin A 1 on kidney pathology and function remain to be determined, these findings highlight the potential benefits of modulating autophagy during cold preservation.…”

Autophagy in Kidney Health and Disease

“…It inevitably occurs during kidney transplantation, and the initial extent of I/R injury significantly affects the function of graft. Activation of autophagy in tubular cells during I/R injury was demonstrated in cell cultures and in animal models of I/R injury (11,23,30,31,41,79,85,93,102), and increased autophagosomes were observed in biopsy specimens from human transplanted kidney (79). In regard to the question whether autophagy provides protection or contributes to the tubular damage from I/R injury, there are both lines of evidence.…”

“…The inhibition of autophagy using autophagy inhibitor 3-MA or Atg7 siRNA significantly reduced ROS (hydrogen peroxide) induced cell death in proximal tubular epithelial cell line (HK-2) (79). Inhibition of autophagy flux using bafilomycin A1 also significantly reduced apoptotic cell death and caspase activity in kidneys with prolonged ischemic preservation (85).…”

Molecular Mechanisms Underlying the Neuroprotective Effect of Hypothermia in Cerebral Ischemia

“…Recently, it was reported that delayed neuronal death occurring in the CA1 pyramidal layer of the gerbil hippocampus after ischemia is apoptotic in nature and autophagosomes/autolysosomes are abundant in these neurons before DNA fragmentation (Xu and Zhang, 2011), i.e., under ischemic conditions, autophagy follows the activation of the mitochondrial pathway of apoptosis; cytochrome c is released from mitochondria, and caspase-9/caspase-3 are activated. Turkmen et al (2011) recently showed that autophagy and autophagic flux are reduced in cold ischemic kidneys treated with bafilomycin A1. Reduced autophagy and autophagic flux were associated with a significant reduction in apoptotic cell death.…”