NGFI-B在大鼠抗胸腺细胞血清性肾炎模型肾组织的表达

目的:观察NGFI-B mRNA在大鼠抗胸腺细胞血清性肾炎(anti-thymocyte serum induced nephritis,AT- SN)不同发病时相肾组织的表达水平,从基因层面上探讨ATSN大鼠肾小球系膜细胞(mesangial cell,MC)凋亡的可能原因。方法:复制ATSN动物模型,应用RT-PCR分析NCFI-B的表达水平。结果:应用RT-PCR检查,结果显示,实验40min,NGFI-B mRNA表达显著高于对照组,且实验40min,NGFI-B mRNA水平较5d时明显增多。结论:NGFI-B基因表达上调可能与肾小球MC的早期凋亡存在一定的联系。     

Activation of protein kinase Czeta mediates luteinizing hormone- or forskolin-induced NGFI-B expression in preovulatory granulosa cells of rat ovary

We have previously demonstrated that luteinizing hormone (LH) induces a rapid and transient expression of NGFI-B in the ovary. In this report, we investigated the signaling pathway for LH- and forskolin-induced NGFI-B expression in cultured rat granulosa cells of preovulatory follicles. LH- or forskolin-induced NGFI-B expression was suppressed by high dose of protein kinase C (PKC) inhibitor RO 31-8220 (10 μM), but not by low doses RO 31-8220 (0.1–1.0 μM) or adenylate cyclase inhibitor MDL-12,300A, implicating the involvement of atypical PKCs. Kinase assay revealed that LH treatment of granulosa cells resulted in a rapid stimulation of atypical PKCζ activity. Interestingly, like LH, forskolin was also able to activate PKCζ. Treatment with the cell-permeable PKCζ-specific inhibitor pseudosubstrate peptide inhibited LH-or forskolin-induced NGFI-B expression, indicating the essential role of PKCζ. Consistent with this promise, in granulosa cells depleted of diacylglycerol sensitive PKCs by prolonged treatment with tetradecanoylphobol-13-acetate, LH or forskolin could still induce NGFI-B expression, and RO 31-8220 or the PKCζ pseudosubstrate peptide inhibited LH- or forskolin-induced NGFI-B expression. Furthermore, overexpression of dominant-negative PKCζ in primary granulosa cells using a replication-defective adenovirus vector resulted in the suppression of LH- or forskolin-induced NGFI-B expression. Our findings demonstrate that PKCζ, which is activated by LH or forskolin, contributes to the induction of NGFI-B in granulosa cells of preovulatory follicles.     

mRNA expression of the Nurr1 and NGFI-B nuclear receptor families following acute and chronic administration of methamphetamine

Nur-related 1 (Nurr1) and nerve growth factor inducible-B (NGFI-B) constitute closely related subgroups of the nuclear receptor superfamily. One to three hours after 4 mg/kg acute methamphetamine (METH) administration, the levels of Nurr1 mRNA were significantly higher in the prelimbic (PrL), primary motor (M1) and primary somatosensory (S1) cortices and ventral tegmental area (VTA), as compared with the basal level. Pretreatment with 0.5 mg/kg of SCH23390 prevented the acute METH-induced increase in Nurr1 mRNA levels in these brain regions. One to three hours after 4-mg/kg acute METH administration, the levels of NGFI-B mRNA increased significantly in the PrL, M1, S1, striatum, and nucleus accumbens core (AcbC). Pretreatment with either 0.5 mg/kg of MK-801 or 0.5 mg/kg of SCH23390 prevented the acute METH-induced increase in NGFI-B mRNA levels in these brain regions. The levels of mRNAs were determined 3 h after a challenge injection of either saline or 4 mg/kg METH at the three-week withdrawal point in rats which had previously been exposed to either saline or METH (4 mg/kg/day) for 2 weeks. After the saline challenge, the group chronically exposed to METH displayed significantly higher levels of Nurr1 mRNA in the PrL, S1 and VTA, and of NGFI-B mRNA in the PrL, M1, S1, striatum and AcbC than did the group chronically treated with saline. The groups chronically exposed to METH failed to increase Nurr1 mRNA in the VTA, and NGFI-B mRNA in the AcbC, when challenged with 4 mg/kg METH. These results suggest that Nurr1 and NGFI-B mRNA play differential roles upon exposure to METH.     

Dexamethasone induces cell death which may be blocked by NMDA receptor antagonists but is insensitive to Mg2+ in cerebellar granule neurons

Since dexamethasone may elevate the Ca2+ influx through NMDA receptors, we have investigated mechanisms of dexamethasone toxicity in rat cerebellar granule neurons. Dexamethasone concentrations over 0.1 microM induced cell death that reached about 20% of the death induced by glutamate. Dexamethasone-induced cell death was reduced by more than 80% by the mineralocorticoid antagonist RU 28318 or the NMDA receptor antagonists MK 801 and CGP 39551, whereas RU 28318 rescued only approximately 30% of cells treated with glutamate, indicating that dexamethasone requires NMDA receptors to induce acute neuronal toxicity and that a fraction of the neurons showed this toxicity. Mg2+ reduced the cell death induced by glutamate at potassium concentrations of 1 mM and 5 mM, but not at 25 mM. In contrast, cell death induced by dexamethasone was not significantly reduced by Mg2+ in any of the potassium concentrations. Both glutamate and dexamethasone induced toxicity with translocation of the apoptosis inducer NGFI-B to the mitochondria seen after 30 min-2 h concomitant with activation of apoptosis inducing factor (AIF) and caspase-3. In conclusion, dexamethasone induces a rapid toxicity which is blocked by NMDA receptor antagonists other than Mg2+, and involves mitochondrial apoptosis inducer NGFI-B.     

Long-term influence of an initial exposure to alcohol on the rat hypothalamic-pituitary axis

OBJECTIVE: We have previously shown that adult male rats injected with alcohol daily for 3 consecutive days displayed a significantly blunted ACTH to a second alcohol injection, given 3 to 7 days later. The purpose of the present work was to determine the maximum duration over which the ACTH response remained blunted after an initial alcohol treatment. METHODS: Male rats were exposed to alcohol (intragastrically or via vapors for 4 hr) on three consecutive days, starting when they were 22 (group A), 34 (group B), or 50 days old (group C). Control animals were injected with the vehicle intragastrically or kept in chambers through which normal air was circulated. At 60 days of age, the animals were injected with the vehicle or alcohol (4.5 g/kg intragastrically) to determine whether the initial treatment had long-term consequences on the ACTH response to a second alcohol challenge. RESULTS: Rats of group C, pretreated with alcohol via intragastric injections or vapors, all exhibited a blunted ACTH response to the second acute alcohol challenge. In contrast, the second alcohol challenge only attenuated ACTH responses in rats of group B that had received intragastric injections, but not vapors. Group A showed a comparable response to acute intragastric alcohol injection at 60 days of age regardless of whether they had been preexposed to the drug. This was not due to a lack of neuroendocrine response because alcohol vapors significantly increased plasma ACTH levels and up-regulated paraventricular nucleus neuronal activity regardless of the age at which it was initially administered. CONCLUSIONS: Repeated (daily for 3 consecutive days) administration of alcohol by the gastric route induces a long-lasting (up to 24 days) but not permanent blunting of the ACTH response to a second (acute) alcohol challenge. The fact that alcohol delivered by inhalation only caused a relatively brief (相似文献