A disintegrin and metalloproteinase domaincontaining protein 12 (ADAM12) belongs to the ADAM family of transmembrane proteins. Via proteolysis, cell adhesion, cellcell fusion, cellmatrix interaction and membrane protein shedding, ADAM proteins are involved in normal brain development,
and also in cancer genesis and progression, and in inflammation. Therefore, neurobiological research focusing on this protein is increasing. Nitric oxide (NO), which is endogenously produced by NO synthases (NOS), is associated with glial tumors. However, knockout of NOS produces only
limited antitumor effects. The present study analyzed the expression of ADAM12 in the cortex and hippocampus of C57/BL6 wildtype mice, and endothelial NOS, neuronal NOS (nNOS) or inducible NOS (iNOS)deficient (/) mice, at different stages of development. Expression of ADAM12 was quantified
using immunoblot analysis of cortical and hippocampal tissue samples from fetal, neonatal (5 days postnatal), adult (12 weeks old) or >1 year old mice. Using reverse transcriptionquantitative polymerase chain reaction, ADAM12 expression was analyzed in cultured N9, OLN93,
C6 and PC12 cells, representing the four main cell types in the brain, following NOS inhibition. ADAM12 expression was low in all mouse genotypes and regions of the brain, and in fetal and neonatal mice, an increase in expression was observed with increasing age. The highest levels of expression
were observed in the cortex of adult mice, iNOS/ mice of >1 year and wildtype mice, and in the hippocampus of adult and iNOS/ mice of >1 year. By contrast, ADAM12 expression was lowest in adult nNOS/ mice. Inhibition of NOS using NωNitroLarginine methyl ester hydrochloride,
induced ADAM12 mRNA expression in N9 and PC12 cell lines. Inhibition of NOS using LN6(1Iminoethyl)lysine dihydrochloride, induced ADAM12 mRNA expression in N9 and C6 cell lines. No change in ADAM12 expression was observed in OLN93 cells following NOS inhibition. ADAM12 expression in mouse
hippocampus and cortex samples demonstrated considerable variation during development, with a marked increase observed in adult and >1 year old mice, compared with that in fetal and neonatal mice.
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Document Type: Research Article
Institute of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, ErnstMoritzArndt University, Greifswald D17475, Germany
Clinic of Psychiatry, Psychotherapy and Psychosomatic Medicine, OttovonGuericke University, Magdeburg D39120, Germany
Institute of Biochemistry and Cell Biology, OttovonGuericke University, Magdeburg D39120, Germany
Publication date: August 1, 2015
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Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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