Neuroglobine

The neuroglobine is a globine of storage and transport of oxygen in the Nervous system. For this reason, it presents many analogies with the Myoglobine: monomeric structure, strong affinity for oxygen. Thus, the neuroglobine facilitates the transport of oxygen towards the Mitochondrie S of the nervous cells and plays a fundamental role in the protection of the Neuron S in conditions of Hypoxie.

Discovered neuroglobine

The existence of a globine in the nervous cells was known in certain invertebrates (Mollusques and towards in particular) but had not been highlighted up to that point in the higher animals. The way in which the neuroglobine was discovered is particularly interesting and famous good an new approach of research in Physiologie based on the study of the Génome. Indeed, to seek existence such globine, the researchers of the institute of zoology and molecular department of genetics of the university of Mainz (Germany) worked starting from data banks giving the sequencing of fragments of human and murine DNA. Knowing the structure of the Gene S of the Hemoglobin and the Myoglobin, they sought in the data banks, the sequences of DNA presenting of the analogies with these genes. From these sequences of DNA, they could cloner and séquencer a human gene carried by the Chromosome 14 and coding a protein of 151 Amino-acid , pertaining to the family of the globines, but distinct from hemoglobin and myoglobin. The murine gene correspondent could also be identified and has a rate of identity of 94% with its human analog.

Form of gene of the neuroglobine

By several techniques of molecular Hybridization, the researchers of the university of Mainz could seek ARN messenger produced by gene of the neuroglobine in various fabrics. thus the expression of this gene was highlighted at the level of the brain, mainly at the level of the frontal Lobe, in the Thalamus and the Noyaux under-thalamiques. In addition, the expression of this gene was weaker (10 to 20%) in the colon, the lungs, or even tiny (<10%) or absent from other fabrics. Thus this globine was primarily present in the Nervous system, the authors allotted to him the name of neuroglobine . the study of the recombining neuroglobines (which obtaining is easier than by purification), watch which they fix the reversible oxygen of manner, which is a general property for the majority of the Globines. Affinity with oxygen for the neuroglobine (oxygen pressure with 50% of saturation (P50) = 1 to 2 Torr) is much higher than that for the Hémoglobine (26 torr) and similar to that of the Myoglobine (1 torr).

The spectroscopic study shows that O2 and CO bind to the neuroglobine by a mechanism in three stages:

$Fe {\ color {Blue} HisE_7} + {\ color {red} L} \ leftrightarrow \ Fe + {\ color {Blue} HisE_7} + {\ color {red} L} \ leftrightarrow \ Fe {\ color {red} L} + {\ color {Blue} HisE_7}$ (L is O2 or CO)

The first dissociation between Fe and HisE7 (ligand endogenous) constitute the limiting stage (Koff = between 4.5 and 8.2 X 10 ³/S). On the other hand, the constant of first order association between the Fe and L are important (Kon = between 1,3 and 2,5 X 10 ⁸/S). Apparent affinities of the exogenic ligands (O2 and CO) seem identical to those obtained with the Myoglobine and the chains isolated α and β from the Hémoglobine.

Neuroglobine and hypoxia

In favor of his property to fix oxygen reversibly, one can notice that the cerebral zones where the expression of the neuroglobine is relatively weak are more sensitive to the Hypoxie whereas those where its expression is higher are more resistant. For example, the intermediate duration of the Ischaemia necessary to produce half of the maximum damage is of 19,1 min for the cerebral Cortex and of 12,7 min for the Hippocampe, and the expression of the neuroglobine in the cerebral cortex is approximately 4 times higher than in the hippocampus. The sensiblity of the hippocampus to the hypoxia can explain at the man, among the after-effects of ischemic accidents severe or intoxication with CO, the disorders of memory.

The results obtained by the team of the Buck Institute of research on veillissement (California, the USA) support the concept that the neuroglobine provides a function of facilitated transport and storage of oxygen in the neurons. This team studied the effect of the deprivation of oxygen on the cellular Viabilité of murine neurons in culture by using markers of the function mitochondriale, of integrity of the membrane and cellular activation of Mort. In a very significant way, the cellular consequences of the hypoxia were more important for the neurons of which the synthesis of the neuroglobine at inhibited summer with 50% by a ARN anti-direction. Conversely, the surexpression of gene of the neuroglobine by Transfection is accompanied by better viabilté cellular under the conditions of hypoxia.

The neuroglobine proved to have a specific effect on the aggression caused by the Hypoxie and did not show a general action of cellular protection. Indeed, the blockage of its expression and its surexpression it is shown without effect on the markers of viability of cells subjected to other agents having a cellular toxicity like the staurosporine or the nitroprusside of sodium, a donor of NO.

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