Kidney Ischaemia-Reperfusion Injury and Polyribosome Structure

Abstract

Background: Inhibition of protein synthesis and polyribosome disaggregation are the early events in cell injury provoked by various pathogenic mechanisms, including energy depletion. Polyribosome disaggregation might be expected to occur during ischaemia-reperfusion injury due to ischaemic energy depletion, but also due to detrimental effects of reactive oxygen species on various macromolecules and cellular structures. Methods: Mouse kidney ischaemia-reperfusion injury was provoked by temporary clamping of the renal artery. The polyribosome sedimentation pattern was analyzed by sucrose density centrifugation of kidney postmitochondrial supernatant. Results and Conclusions: Ischaemia for 5 min in the mouse kidney provoked polyribosome disaggregation and an increase of monomer ribosome fraction which was augmented during 10–360 min of reperfusion. Recovery of polyribosome aggregates appeared between 6 and 24 h of reperfusion. Cycloheximide pretreatment prevented only polyribosome disaggregation caused by ischaemia and not that caused by reperfusion. This indicates different mechanisms of polyribosome disaggregation during ischaemia and reperfusion. It probably occurs in the former due to inhibition of initiation of translation, resulting in accumulation of unprogrammed monomer ribosomes, and in the latter due to the splitting of mRNA and breakdown of polyribosomes. Reperfusion did not increase ribonuclease activity in kidney cytosol, but increased the tissue concentration of malonaldehyde, indicating an augmentation in oxygen free radical generation. Possibly these may have caused a non-enzymatic breakdown of polyribosomes. However, pretreatment with allopurinol did not prevent polyribosome breakdown during ischaemia-reperfusion injury.

Effect of mutation of amino acids 246–251 (KRKHKK) in HSP72 on protein synthesis and recovery from hypoxic injury

“…Similarly, HSP72 is associated with the ribosome in the thermotolerant cell that has undergone a brief heat shock (2). Polysomes disassociate under conditions of ischemia and other similar injury (12,19,21). In the current experiments, overexpression of WT HSP72 was associated with preservation of polysomes and better recovery of protein synthesis than in the nontransfected C2C12 cells.…”

Acute Kidney Injury Associated with Cardiac Surgery: a Comprehensive Literature Review

“…Other stimuli, such as endotoxemia, tissue injury, operative trauma, and pre-existing left ventricular dysfunction, could possibly play a role in activation of the immune system. Proinflammatory cytokines and free radicals are produced, leading to renal tubular injury, which is further enhanced by the activation of neutrophils, macrophages, and migration of lymphocyte to renal parenchyma [18] . Ischemia-reperfusion injury occurs and induces the production of reactive oxygen species (ROS).…”

MIF-2/D-DT enhances proximal tubular cell regeneration through SLPI- and ATF4-dependent mechanisms

“…Depression of protein synthesis is characteristic of kidneys suffering from ischemic reperfusion (58). A number of mechanisms can lead to translation initiation inhibition, including stress to the endoplasmic reticulum, which activates specific regulatory pathways leading to the phosphorylation of the eIF2␣ (62).…”