DI-UMONS : Dépôt institutionnel de l’université de Mons

Recherche transversale
(titres de publication, de périodique et noms de colloque inclus)
2010-11-16 - Colloque/Article dans les actes avec comité de lecture - Anglais - 1 page(s)

Satriano J, Decleves Anne-Emilie , Vallon V, Sharma K, "AMPK Induction is Protective in Ischemia-Reperfusion Injury." in Meeting of the American Society of Nephrology, 21, 343A, Denver, US-CO

  • Codes CREF : Histologie (DI3212), Sciences biomédicales (DI3200), Néphrologie - urologie (DI3325), Physiologie pathologique (DI3250), Métabolisme (DI3223)
  • Unités de recherche UMONS : Biochimie métabolique et moléculaire (M122)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé)
  • Centres UMONS : Centre de Recherche UMONS-Ambroise Paré (UMHAP)

Abstract(s) :

(Anglais) Ischemia reperfusion (IR) causes a cascade of cellular events prompting cellular damage leading to cell death. A response to ischemia is the activation of AMP-activated protein kinase (AMPK). AMPK induces a number of protective, cell survival mechanisms. We propose that inducing AMPK activity prior to IR could prove beneficial. Sprague-Dawley rats were divided into 4 groups: 1) Control, 2) IR, 3) AMPK inducer, AICAR, 4) IR+AICAR. AICAR (0.1g/kg) was administered 24h prior to ischemia. Three weeks after nephrectomy (all groups) kidney ischemia was performed for 30 min, with reperfusion for 24 hrs. AICAR significantly increased AMPK activity (pAMPK/AMPK ratio: C 1.13±0.32, IR 1.82±0.19, AICAR 2.39±0.35, IR+AICAR 4.15±0.32*, N=4-5 for each group, mean±SEM; * P<0.05 v IR). Immunoblotting showed an increase in autophagy protein LC3-I in AICAR samples (C 3608±174; IR 3687±309, AICAR 6183±285, IR+AICAR 7137±326*; relative densitometric units). During autophagy, cytosolic LC3-I is converted to an active autophagosome bound LC3-II form. LC3-II increases with IR and significantly further in IR+AICAR (C 318±103, IR 1179±111, AICAR 743±144, IR+AICAR 3629±629*). Autophagy rids the cell of damaged proteins and organelles, suppressing oxidative stress and cell death. In accord with increased autophagy we observed a decrease in the apoptotic execution caspase-3 expression in IR with AICAR (C 1353± 100, IR 4286± 246, AICAR 2039± 62, IR+AICAR 3208± 255*). IR decreased the gap junction protein Cx43, limiting the spread of IRI associated signaling molecules, and increased cyclin kinase inhibitor p27KIP1 and ROS generating NOX4 expressions. AICAR significantly attenuated these responses to IR, again implying less extensive injury (Cx43: C 697±104, IR 345±32, AICAR 1258±71, IR+AICAR 544±30*; p27: C 622±151, IR 4983±515, AICAR 1010±80, IR+AICAR 2709±154*; NOX4: C 624±108, IR 4275±665, AICAR 769±130, IR+AICAR 2858±346*). Parallel changes occurred in response to the AMPK agonist, metformin. There are currently no clinical procedures in place to safeguard the kidney from IRI. This data implies AMPK induction, in part through induction of autophagy, can provide protective effects in IR.