Cell Line, Tumor ; Cell Proliferation ; Glutaminase

OBJECTIVE: To investigate the underlying molecular mechanisms by which silence information regulator (SIRT) 2 and glutaminase (GLS) in the amygdala regulate social behaviors in autistic rats. METHODS: Rat models of autism were established by maternal sodium valproic acid (VPA) exposure in wild-type rats and SIRT2-knockout ( SIRT2 ^-/-) rats. Glutamate (Glu) content, brain weight, and expression levels of SIRT2, GLS proteins and apoptosis-associated proteins in rat amygdala at different developmental stages were examined, and the social behaviors of VPA rats were assessed by a three-chamber test. Then, lentiviral overexpression or interference vectors of GLS were injected into the amygdala of VPA rats. Brain weight, Glu content and expression level of GLS protein were measured, and the social behaviors assessed. RESULTS: Brain weight, amygdala Glu content and the levels of SIRT2, GLS protein and pro-apoptotic protein caspase-3 in the amygdala were increased in VPA rats, while the level of anti-apoptotic protein Bcl-2 was decreased (all P<0.01). Compared with the wild-type rats, SIRT2 ^-/- rats displayed decreased expression of SIRT2 and GLS proteins in the amygdala, reduced Glu content, and improved social dysfunction (all P<0.01). Overexpression of GLS increased brain weight and Glu content, and aggravated social dysfunction in VPA rats (all P<0.01). Knockdown of GLS decreased brain weight and Glu content, and improved social dysfunction in VPA rats (all P<0.01). CONCLUSIONS The glutamate circulatory system in the amygdala of VPA induced autistic rats is abnormal. This is associated with the upregulation of SIRT2 expression and its induced increase of GLS production; knocking out SIRT2 gene or inhibiting the expression of GLS is helpful in maintaining the balanced glutamate cycle and in improving the social behavior disorder of rats.
Animals ; Rats ; Amygdala/metabolism* ; Autistic Disorder/metabolism* ; Behavior, Animal ; Disease Models, Animal ; Glutamates/metabolism* ; Glutaminase/metabolism* ; Sirtuin 2/metabolism* ; Social Behavior

glutaminase were increased their expression after the administration of FGF-5. The pinin, ribosomal protein S29, proliferation-associated 2G4, protein phosphatase 1G, PICTAIRE protein kinase 1, cell division cycle 25A, keratin 7, 15, and 17, bone morphogenetic protein 1 and 7, and placental growth factor were In conclusion, FGF-5 was a potent mitogen for human fibroblasts, but FGF-7 was not. FGF-5 could induce FGF-7 expression, but FGF-7 inhibited FGF-5 expression. Thus, the gingival hyperplasia in the immunosuppressed patients seemed to be occurred via the action of FGF-5. The role of FGF-7 that was expressed in these patients might be late events after the expression of FGF-5.]]>
Bone Morphogenetic Protein 1 ; Carrier Proteins ; Cell Count ; Cell Cycle ; DNA, Complementary ; Fibroblasts ; Gingival Hyperplasia ; Glutaminase ; Humans ; Keratin-7 ; Oligonucleotide Array Sequence Analysis ; Organ Transplantation ; Protein Kinases ; Protein Phosphatase 1 ; Receptor, Epidermal Growth Factor ; Ribosomal Proteins ; Transcription Factors ; Transplants