Neuroglobin mitigates mitochondrial impairments induced by acute inhalation of combustion smoke in the mouse brain

Falih Murat Gorgun, Ming Zhuo, Shilpee Singh, Ella W. Englander

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Context: Acute inhalation of combustion smoke adversely affects brain homeostasis and energy metabolism. We previously showed that overexpressed neuroglobin (Ngb), neuron specific globin protein, attenuates the formation of smoke inhalation-induced oxidative DNA damage, in vivo, in the mouse brain, while others reported protection by Ngb in diverse models of brain injury, mainly involving oxidative stress and hypoxic/ischemic insults. Objective: To determine to what extent elevated Ngb ameliorates post smoke-inhalation brain bioenergetics and homeostasis in Ngb overexpressing transgenic mouse. Methods: Smoke inhalation induced changes in bioenergetics were measured in the wild type and Ngb transgene mouse brain. Modulations of mitochondrial respiration were analyzed using the Seahorse XF24 flux analyzer and changes in cytoplasmic energy metabolism were assessed by measuring enzymatic activities and lactate in the course of post smoke recovery. Results: Cortical mitochondria from Ngb transgene, better maintained ATP synthesis-linked oxygen consumption and unlike wild type mitochondria did not increase futile oxygen consumption feeding the proton leak, reflecting lesser smoke-induced mitochondrial compromise. Measurements revealed lesser reduction of mitochondrial ATP content and lesser compensatory increases in cytosolic energy metabolism, involving pyruvate kinase and lactate dehydrogenase activities as well as cytosolic lactate levels. Additionally, induction of c-Fos, the early response gene and key neuronal stress sensor, was attenuated in Ngb transgene compared to wild type brain after smoke. Conclusion: Considered together, these differences reflect lesser perturbations produced by acute inhalation of combustion smoke in the Ngb overexpressing mouse, suggesting that Ngb mitigates mitochondrial dysfunction and neurotoxicity and raises the threshold of smoke inhalation-induced brain injury.

Original languageEnglish (US)
Pages (from-to)361-369
Number of pages9
JournalInhalation toxicology
Volume26
Issue number6
DOIs
StatePublished - May 2014

Keywords

  • Bioenergetics
  • Brain
  • Mitochondria
  • Neuroglobin
  • Oxygen consumption
  • Smoke inhalation

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Fingerprint Dive into the research topics of 'Neuroglobin mitigates mitochondrial impairments induced by acute inhalation of combustion smoke in the mouse brain'. Together they form a unique fingerprint.

  • Cite this