Sunday, January 08, 2006

Musings on Carbon Monoxide

Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3497-500. Epub 2003 Mar 5.

Click here to read Click here to read Click here to read
Neuroglobin protects the brain from experimental stroke in vivo.

Sun Y, Jin K, Peel A, Mao XO, Xie L, Greenberg DA.

Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA.

Neuroglobin (Ngb) is an O(2)-binding protein localized to cerebral neurons of vertebrates, including humans. Its physiological role is unknown but, like hemoglobin, myoglobin, and cytoglobin/histoglobin, it may transport O(2), detoxify reactive oxygen species, or serve as a hypoxia sensor. We reported recently that hypoxia stimulates transcriptional activation of Ngb in cultured cortical neurons and that antisense inhibition of Ngb expression increases hypoxic neuronal injury, whereas overexpression of Ngb confers resistance to hypoxia. These findings are consistent with a role for Ngb in promoting neuronal survival after hypoxic insults in vitro. Here we report that in rats, intracerebroventricular administration of an Ngb antisense, but not sense, oligodeoxynucleotide increases infarct volume and worsens functional neurological outcome, whereas intracerebral administration of a Ngb-expressing adeno-associated virus vector reduces infarct size and improves functional outcome, after focal cerebral ischemia induced by occlusion of the middle cerebral artery. We conclude that Ngb acts as an endogenous neuroprotective factor in focal cerebral ischemia and may therefore represent a target for the development of new treatments for stroke.

BrooklynDodger comments: The Sago mine tragedy refocuses attention on carbon monoxide.

When the Dodger was in toxicology school, CO toxicity was mechanized as hypoxia arising from CO competing for hemoglobin binding sites. Even then we knew there was myoglobin - remember sperm whale myoglobin as the early illustration of 3-D protein structure deduced from x-ray chrystallography? But we weren't taught to think about myoglobin's role, which was binding oxygen in muscle cells, and Dodger guesses donating that bound oxygen to metabolic processes.

The lowest dose human health effect of CO is potentiating irregular heart beat among people with pre existing ischemia. To the Dodger, it would appear more plausibly a direct effect of CO on the muscle than an indirect effect of low oxygen. The CO is carried to the tissue by hemoglobin.

So a brief tour through medline revealed a new name, "neuroglobin," which is the same deal. Maybe it's CO binding to neuroglobin rather than myoglobin which causes these heart rhythm effects.

No comments: