The comparison of mouse full metallothionein‐1 versus α and β domains and metallothionein‐1‐to‐3 mutation following traumatic brain injury reveals different biological motifs |
| |
Authors: | Yasmina Manso Montserrat Serra Gemma Comes Mercedes Giralt Javier Carrasco Neus Cols Milan Vašák Pilar González‐Duarte Juan Hidalgo |
| |
Affiliation: | 1. Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Animal Physiology Unit, Faculty of Biosciences, Autonomous University of Barcelona, Barcelona, Spain;2. Department of Chemistry, Faculty of Sciences, Autonomous University of Barcelona, Barcelona, Spain;3. Department of Genetics, Faculty of Biology, University of Barcelona, Barcelona, Spain;4. Institute of Biochemistry, University of Zürich, Switzerland |
| |
Abstract: | Traumatic injury to the brain is one of the leading causes of injury‐related death or disability, but current therapies are limited. Previously it has been shown that the antioxidant proteins metallothioneins (MTs) are potent neuroprotective factors in animal models of brain injury. The exogenous administration of MTs causes effects consistent with the roles proposed from studies in knock‐out mice. We herewith report the results comparing full mouse MT‐1 with the independent α and β domains, alone or together, in a cryoinjury model. The lesion of the cortex caused the mice to perform worse in the horizontal ladder beam and the rota‐rod tests; all the proteins showed a modest effect in the former test, while only full MT‐1 improved the performance of animals in the rota‐rod, and the α domain showed a rather detrimental effect. Gene expression analysis by RNA protection assay demonstrated that all proteins may alter the expression of host‐response genes such as GFAP, Mac1 and ICAM, in some cases being the β domain more effective than the α domain or even the full MT‐1. A MT‐1‐to‐MT‐3 mutation blunted some but not all the effects caused by the normal MT‐1, and in some cases increased its potency. Thus, splitting the two MT‐1 domains do not seem to eliminate all MT functions but certainly modifies them, and different motifs seem to be present in the protein underlying such functions. © 2010 Wiley‐Liss, Inc. |
| |
Keywords: | Traumatic brain injury full MT‐1 MT‐1 domains MT‐1‐to‐MT‐3 mutation |
|
|