Multi‑faceted roles of cathepsins in ischemia reperfusion injury (Review)

Abstract

Cathepsins are one of the most abundant proteases within the lysosomes with diverse physiological effects ranging from immune responses, cell death and intracellular protein degradation. Cathepsins are involved in extracellular and systemic functions such as systemic inflammation and extracellular matrix degradation. Ischemia reperfusion (IR) injury is responsible for numerous diseases including myocardial infarction, acute kidney injury, stroke and acute graft failure after transplant surgery. Inflammation plays a major role in the reperfusion phase of IR injury and previous research has shown that cathepsins are key mediators of the inflammation cascade as well as apoptosis. Taken together, cathepsins modulation could provide potential therapeutic approaches to attenuate IR injury. The present review summarized the current understanding of various cathepsin subtypes, their major physiologic functions, their roles in multi-organ IR injury and detailed selective cathepsin inhibitors with therapeutic potential. Contents1. Introduction 2. Cysteine cathepsins 3. Aspartic cathepsins 4. Serine cathepsins 5. Roles for cathepsins in ischemia reperfusion (IR) injury 6.

Inhibitors of NLRP3 Inflammasome in Ischemic Heart Disease: Focus on Functional and Redox Aspects

“…Another harmful aspect induced by early reperfusion is inflammatory damage mediated by the activation of mast cells and neutrophils, whose products act as chemoattractants for other leukocytes [39]. Recently cathepsins, proteases involved in multiple pathophysiological roles, have attracted the attention of researchers.…”

“…Recently cathepsins, proteases involved in multiple pathophysiological roles, have attracted the attention of researchers. In particular, cathepsin G, a modulator of neutrophil chemoattractant, induces morphological modifications that break focal adhesion and intracellular contacts with cardiomyocytes and is involved in MIRI [39,40]. Indeed, cathepsin G inhibition with DCCI (dual inhibitor of cathepsin G and chymase) limits MIRI and damages [41].…”

Mendelian randomization analyses explore the relationship between cathepsins and stroke

“…They are pivotal in various normal and pathological cellular processes, including antigen presentation, autophagy, recycling of growth factor receptors, apoptosis, cell cycle regulation, and degradation of the extracellular matrix [6] . Through these diverse mechanisms, different cathepsins contribute signi cantly to the onset and progression of stroke [7] .…”

Desarrollo de una vacuna a base de nanopartículas

“…El mecanismo de activación de la inmunidad innata del adyuvante Alum (sales de aluminio), ampliamente empleado en vacunas para humanos, es precisamente mediante la activación del inflamosoma NLRP3 60,119 .…”

“…Si bien las Np son estables a pH levemente ácido (apenas por debajo del fisiológico), sostenemos que en este entorno intra-lisosomal la Np se desarma, probablemente de manera parcial, y las cargas positivas que presentan los polímeros desestabiliza al lisosoma a causa de una posible despolarización de la membrana. Esto genera la ruptura parcial de su membrana permitiendo la liberación del contenido al citosol, en el cual se encuentran proteasas de la familia de las catepsinas 97,106,119 . Este proceso se denomina permeabilización de la membrana lisosomal 96,133,134 .…”