Palmeira 2019 MiP2019

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Carlos Palmeira
Prevention of ischemia/reperfusion injury: effects of a soluble adenylyl cyclase inhibitor LRE1.

Link: MiP2019

Rolo AP, Teodoro JS, Machado I, Steegborn C, Palmeira CM (2019)

Event: MiP2019

COST Action MitoEAGLE

Ischemia/reperfusion injury (IR) is a common deleterious process that occurs after an ablation and restoration of circulation to an organ, and typically hinges on a surge of reactive oxygen species (ROS) generation, leading to cellular injury and tissue failure. Given the ubiquitous role of mitochondria as a key organelle to the survival to IR, strategies that directly target mitochondria and prime them towards stress handling might prove clinically invaluable. In fact, mitochondrial pre-conditioning has shown promising results, only marred by the need of surgical intervention. As such, a pharmacological intervention that could mimic surgical mitochondria precondition could improve mitochondrial function in a setting of rodent model of hepatic IR. Therefore, we tested LRE1 (a sAC inhibitor) administration before I/R.

Male Wistar rats were subjected to a portal vein injection with LRE1 previous to surgical IR. After 24h, liver mitochondria were isolated and several metabolic parameter assessment tests were conducted.

LRE1 was able to revert several evaluated parameters, including calcium tolerance, ROS generation and OXPHOS activity. It is clear that, by acting through different mechanisms, the inhibitor was able to acclimatize mitochondria to the insult.

It is apparent from our data that, by manipulating the generation of cAMP, we could prime mitochondria for IR injury, leading to prospective clinical investigation of the feasibility of this inhibitor for human utilization.


Bioblast editor: Plangger M


Labels: MiParea: Pharmacology;toxicology 

Stress:Ischemia-reperfusion  Organism: Rat  Tissue;cell: Liver  Preparation: Isolated mitochondria 





Affiliations and support

Anabela Pinto Rolo(1,2), João Soeiro Teodoro(1,2), Ivo Machado(1,2), Clemens Steegborn(3), and Carlos Marques Palmeira(1,2)
  1. Dept Life Sciences
  2. Center Neurosciences Cell Biology; Univ Coimbra, Portugal
  3. Dept Biochemistry, Univ Bayreuth, Germany
Supported by PTDC/BIM-MEC/6911/2014 and POCI-01-0145-FEDER-007440. JST is a recipient of a FCT grant(SFRH/BPD/94036/2013).