Dias 2019 MiPschool Coimbra

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Candida Dias
Protective effect of nitrite in brain ischemia/reperfusion via modulation of mitochondrial respiration.

Link: MitoEAGLE

Dias C, Lourenco CF, Barbosa RM, Ledo AM, Laranjinha J (2019)

Event: MiPschool Coimbra 2019


Nitrite, once considered an inert metabolic endpoint of nitric oxide (•NO), has more recently emerged as a metabolic precursor of •NO in vivo. This alternative source of •NO may play a critical role in the brain under emergency conditions such as ischemia, when enzymatic •NO production is hindered due to lack of oxygen. Evidence shows that nitrite is protective in situations of ischemia/reperfusion and appears to be beneficial in aging and neurodegeneration. Most relevantly, nitrite concentration in vivo can be modulated by diet through the ingestion of nitrate rich foods, being generally associated with increased longevity and lower incidence of cardiovascular disease.

One putative target for nitrite´s protective bioactivity in ischemia is through modulation of mitochondrial respiration. We used high-resolution respirometry to determine the effects of nitrite on brain tissue respiration in conditions of ischemia/ reperfusion. We applied an in vitro ischemia/reperfusion protocol to permeabilized rat hippocampal tissue and determined the differences of complex I supported respiration in the presence and absence of nitrite.

While under control (no nitrite) conditions, a significant increase in the respiration rate is observed upon re-oxygenation (“oxidative burst”), in the presence of nitrite (10 μM), this burst is abolished. This inhibition may prevent the increased production of reactive oxygen species associated with this oxidative burst and may be one of the mechanisms through which nitrite is protective during brain ischemia.

Future studies are focused on confirming nitrite reduction to •NO as a requirement for the inhibition of the oxidative burst as well as pin-pointing the site of nitrite/•NO bioactivity within the mitochondrial respiratory chain.

Bioblast editor: Plangger M O2k-Network Lab: PT Coimbra Laranjinha J

Labels: MiParea: Respiration, Exercise physiology;nutrition;life style, Pharmacology;toxicology 

Stress:Ischemia-reperfusion  Organism: Rat  Tissue;cell: Nervous system  Preparation: Permeabilized tissue 

HRR: Oxygraph-2k 

Affiliations and support

Dias C(1,2), Lourenço CF(1,2), Barbosa RM(1,2), Ledo A(1,2), Laranjinha J(1,2)
  1. Center Neuroscience Cell Biology
  2. Fac Pharmacy; Univ Coimbra, Portugal. - [email protected]
Funding: FEDER through COMPETE and FCT under the projects UID/NEU/04539/2019, POCI-01-0145-FEDER-029099, CENTRO-01-0145-FEDER-000012-HealthyAging2020 by the Centro 2020 Regional Operational Program, and PD/BD/114371/2016.