ABSTRACT
ADAM metalloprotease-disintegrins mediate cell adhesion, proteolytic processing, and signal transduction. In the present study, the mRNA levels of ADAM9, ADAM10, and ADAM15 were examined in rat brain after kainic acid (KA)-induced status epilepticus. ADAM9 and ADAM10 expression was induced in dentate gyrus of hippocampus. ADAM15 expression remained unchanged. The spatiotemporal expression of ADAM9 and ADAM10 suggests that their regulation after the KA-induced status epilepticus could be related to neuroprotection.
Subject(s)
Aspartic Acid Endopeptidases/genetics , Dentate Gyrus/metabolism , Disintegrins/genetics , Epilepsy/metabolism , Membrane Proteins/genetics , Metalloendopeptidases/genetics , Metalloproteases/genetics , Status Epilepticus/metabolism , ADAM Proteins , Amyloid Precursor Protein Secretases , Animals , Convulsants , Dentate Gyrus/physiopathology , Disease Models, Animal , Endopeptidases , Epilepsy/chemically induced , Epilepsy/physiopathology , Excitatory Amino Acid Agonists/pharmacology , Kainic Acid , Male , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Status Epilepticus/chemically induced , Status Epilepticus/physiopathology , Up-Regulation/drug effects , Up-Regulation/physiologyABSTRACT
ADAM11 is the prototype member of the predominantly CNS-associated clade of the ADAM metalloprotease-disintegrins that has been implicated in neural adhesion and axon guidance. The present study describes the spatiotemporal expression pattern of the ADAM11 gene in adult and developing mouse, and identifies the cells expressing the gene. In the adult CNS, ADAM11 mRNA was present throughout the forebrain, including different cortical fields and diencephalic nuclei. In brainstem, low to moderate expression was detected in certain midbrain nuclei, while several pontine and medullary nuclei showed a very strong signal. High expression was observed in the cerebellar cortex and spinal cord. In addition, ADAM11 was expressed in ganglia of the peripheral nervous system (PNS), retinae, testes, liver, and at lower levels in epidermal and mucosal epithelia, kidney, and salivary gland. The expression was localized to neurons in all examined CNS and PNS subfields. During pre- and perinatal development, ADAM11 was differentially expressed both in the developing PNS and CNS, as well as in heart, kidney, eyes, and brown fat. The present results suggest a widespread involvement of ADAM11 in neuron-neuron or neuron-glial cell interactions during development as well as in the adult nervous system. They provide novel complementary information to recently accumulated data on CNS integrin gene expression and offer useful clues for further studies of the neural functions of ADAMs and integrins.
Subject(s)
Disintegrins/metabolism , Membrane Proteins/metabolism , Metalloendopeptidases , Nervous System/growth & development , Nervous System/metabolism , Neurons/metabolism , ADAM Proteins , Animals , Animals, Newborn , Disintegrins/genetics , Gene Expression Regulation , In Situ Hybridization , Male , Membrane Proteins/genetics , Mice , Mice, Inbred Strains , Nervous System/embryology , RNA, Messenger/metabolismSubject(s)
Chromosomes, Human, Pair 1/genetics , In Situ Hybridization, Fluorescence , Membrane Proteins/genetics , Metalloendopeptidases/genetics , ADAM Proteins , Chromosome Banding , Genetic Predisposition to Disease/genetics , Humans , Molecular Sequence Data , Neoplasms/genetics , Physical Chromosome MappingABSTRACT
ADAM family of metalloprotease-disintegrins, including enzymes that process TNF-alpha and beta-amyloid precursor protein, has been indicated in neuronal development, but the role of these protease/adhesion/signaling proteins in adult nervous system remains poorly understood. Present study provides a systematic examination of ADAM gene expression in rodent CNS, showing the first quantitative characterization of ADAM mRNA distribution therein. At least 17 ADAM mRNAs were expressed. Individual ADAM mRNAs and their isoforms showed strikingly different expression patterns. Expression of mRNAs for ADAM10, the putative alpha-secretase, and ADAM17 (TACE), also indicated in APP processing, was further characterized using in situ hybridization. Expression of ADAM10 mRNA was widespread, while ADAM17 showed a more restricted pattern. Altogether, the wide and differential expression of ADAM mRNAs suggests versatile roles for ADAMs in the adult CNS.
