REmote ischemic preconditioning prevents sarcolemmal associated protein proteolysis by mmp-2 inhibition

BIN E; ZAOBORNYJ T; GARCES M; D´ANNUNZIO V; BUCHHOLZ B; MARCHINI T; EVELSON P; GELPI RJ; DONATO M

MOLECULAR AND CELLULAR BIOCHEMISTRY

SPRINGER

Lugar: Berlin; Año: 2023

0300-8177

The death of myocytes occurs through different pathways, but the rupture of the plasmamembrane is the key point in the transition from reversible to irreversible injury. In themyocytes, three major groups of structural proteins that link the extracellular andintracellular milieus and confer structural stability to the cell membrane: the dystrophin-associated protein complex, the vinculin–integrin link, and the spectrin-basedsubmembranous cytoskeleton.The objective was to determine if rIPC preserves membrane-associated cytoskeletalproteins (dystrophin and β-dystroglycan) through the inhibition of metalloproteinasetype 2 (MMP-2) activity. A second objective was to describe some of the intracellularsignals of the rIPC, that modify mitochondrial function at the early reperfusion.Methods: Isolated rat hearts were subjected to 30 min of global ischemia and 60 min ofreperfusion (I/R). rIPC was performed by 3 cycles of ischemia/reperfusion in the lowerlimb (rIPC). Results: rIPC significantly decreased the infarct size, induced an Akt/GSK-3 phosphorylation and inhibition of the MPTP opening. rIPC improved mitochondrialfunction, increasing membrane potential, ATP production and respiratory control. I/Rincreased ONOO - production, which activates MMP-2. This enzyme degrades β-dystroglycan and dystrophin and collaborates to sarcolemmal disruption.Conclusion: rIPC attenuates the breakdown of β-dystroglycan and dystrophin throughthe inhibition of MMP-2 activity. Furthermore, rIPC activates different intracellularpathway that involves the an Akt/Gsk3 and MPTP pore with preservation ofmitochondrial function.