RESUMO
The MAGE (Melanoma Associated Antigen) family tumor-specific antigens are shared by a number of histologically different tumors. Till date, only human and mouse MAGE genes have been characterized. Our study describes the first non-mammalian member of MAGE super-family, DMAGE from D. melanogaster. A conceptual translation of the cDNA of DMAGE identifies a putative protein that contains a motif that shares eight out of nine amino acids with the previously identified promiscuous, HLA-A2 restricted antigenic epitope in the C-terminus of human MAGE-B1 and -B2. Similarly, this motif of DMAGE shares seven out of nine amino acids with the same antigenic epitope of human MAGE-A3 and -A12. Thus, the phylogeny of proteins that activate tumor specific T-cells in mammals as unmutated self-proteins began at least 100 million years earlier in evolution than the emergence of the adaptive immune system of higher vertebrates. Northern analysis revealed that DMAGE is a developmentally regulated gene highly expressed in adult fruit fly and in the embryo of D. melanogaster. In contrast, the expression level of the mRNA of DMAGE in fruit fly larva is substantially lower than in embryo and adult fly. We propose that studies of DMAGE on D. melanogaster may help define the function(s) of MAGE super-family genes.
Assuntos
Antígenos de Neoplasias/genética , Drosophila melanogaster/genética , Proteínas de Insetos/genética , Proteínas de Neoplasias/genética , Sequência de Aminoácidos , Animais , Antígenos de Neoplasias/classificação , Sequência de Bases , Evolução Biológica , Clonagem Molecular , Primers do DNA , Drosophila melanogaster/embriologia , Embrião não Mamífero , Biblioteca Gênica , Antígeno HLA-A2 , Larva , Antígenos Específicos de Melanoma , Dados de Sequência Molecular , Proteínas de Neoplasias/classificação , Filogenia , Reação em Cadeia da Polimerase , RNA Mensageiro/análise , Alinhamento de Sequência , Especificidade da EspécieRESUMO
The influence of the CCK-A antagonist devazepide and the CCK-B/gastrin antagonist L-365,260 on the locomotor activity of mice was studied. Devazepide and L-365,260 had opposite effects on spontaneous locomotor activity, and on caerulein- and apomorphine-induced hypomotility in the mouse. Devazepide in high doses (0.1-1 mg/kg IP) reduced spontaneous motor activity, whereas L-365,260 at a high dose (1 mg/kg IP) increased the activity of mice. Devazepide (0.1-10 micrograms/kg) moderately antagonized the sedative effect of apomorphine (0.1 mg/kg SC) and caerulein (25 micrograms/kg SC), whereas L-365,260 (1-10 micrograms/kg) significantly potentiated the actions of dopamine and CCK agonists. Concomitant administration of caerulein (15 micrograms/kg SC) and apomorphine (0.1 mg/kg SC) caused an almost complete loss of locomotor activity in the mouse. Devazepide and L-365,260 (0.1-10 micrograms/kg) were completely ineffective against caerulein-induced potentiation of apomorphine hypomotility. Devazepide in high doses (0.1-1 mg/kg), reducing the spontaneous motor activity of mice, counteracted the motor excitation induced by d-amphetamine (5 mg/kg IP). The CCK agonist caerulein (100 micrograms/kg SC) had a similar antiamphetamine effect. Devazepide (1-100 micrograms/kg) and L-365,260 (1 micrograms/kg) reversed completely the antiamphetamine effect of caerulein. The results of present study reflect apparently distinct role of CCK-A and CCK-B receptors in the regulation of motor activity. The opposite effect of devazepide and L-365,260 on caerulein- and apomorphine-induced hypolocomotion is probably related to the antagonistic role of CCK-A and CCK-B receptor subtypes in the regulation of mesencephalic dopaminergic neurons. The antiamphetamine effect of caerulein is possibly linked to the stimulation of CCK-A receptors in the mouse brain, whereas the blockade of both subtypes of the CCK-8 receptor is involved in the antiamphetamine effect of devazepide.
