Effects of heme oxygenase-1 and its byproduct biliverdin on the mechanisms of endoplasmic reticulum stress in renal ischemia and reperfusion injury

Abstract

Acute kidney injury remains an independent risk factor for mortality and morbidity, increasing the risk of death in patients hospitalized in the intensive care unit. In this context it is well established that inflammation plays an important role in the pathophysiology of the disease. One of the first organelles to cellular stress that suffers is the endoplasmic reticulum (ER), leading to an altered protein folding. The accumulation of unfolded proteins generates a response in RE, which primarily tends to return to homeostasis, which may lead to the production of inflammatory factors and even cell apoptosis, if the stimulus is very strong. Simultaneously to the process of tissue aggression, in recent years it has become clear that the affected organ is also able to assemble various cytoprotective responses, ie, a response intended to limit the damage. Among the various cytoprotective responses, include the induction of expression of heme oxygenase-1 (HO-1). The increased expression of HO-1 promotes the formation of anti-oxidants, anti-apoptotic and immunomodulatory. Thus, the search for greater understanding of these mechanisms of cellular stress response in renal lesions is of great importance, as well as provide more information about processes still remain unclear, allows, by some modular (ns) component (s) of these pathways are developed new therapeutic targets that can restore cellular homeostasis, reducing the acute damage and the consequences in the long term. Thus, we intend to study the role of HO-1 and biliverdin in the modulation of endoplasmic reticulum stress in acute kidney injury using the model of ischemia and reperfusion. For this, we will use conditioned knockout animals to HO-1 and biliverdin reductase genes. Our hypothesis is that the lack of these molecules increases the process of endoplasmic reticulum stress, promoting further inflammation. (AU)