The effects of microwave radiation on expressions of pCREB, CREM, and CBP in the testicular tissue of rats / 解放军医学杂志

Objective To investigate the effects and ascertain the significance of microwave radiation on the expression of phosphorylated cyclic adenosine monophosphate (cAMP)-response element-binding protein (pCREB), cAMP-responsive element modulator (CREM), and CREB-binding protein (CBP) in the testicular tissue of rats. Methods Thirty male Wistar rats were randomly divided into control group (n=5) and radiation group (n=25). Five rats in the radiation group were sacrificed at 6h, 1, 3, 7, and 14d, respectively, after exposure to microwave radiation for 5min, with an average power density of 30mW/cm2. Rats in the control group were sacrificed within 1d without receiving microwave radiation. Expressions and dynamic changes in pCREB, CREM, and CBP in the testicular tissues were examined by immunohistochemistry and Western blotting. Results pCREB, CREM, and CBP were mainly expressed in the sperm nuclei of the seminiferous tubule in the rat testis. pCREB and CBP protein expressions were downregulated from 6h to14d (except for pCREB at 1d) after exposure to microwave radiation (P<0.05 or P<0.01). The expression of CREM was also weakened significantly from 6h to 7d after radiation (P<0.05 or P<0.01). Conclusion The downregulation of pCREB, CREM, and CBP expression may play an important role in the injury of spermatogenic cells caused by microwave radiation.

Role of CREB-binding protein in cyclooxygenase 2 expression in spinal cord in a rat model of neuropathic pain / 中华麻醉学杂志

Objective To evaluate the role of CREB-binding protein (CBP) in cyclooxygenase 2 (COX-2) expression in spinal cord in a rat model of neuropathic pain (NP).Methods Forty male SD rats weighing 220-250 g in which intrathecal catheter was successfully implanted were randomly divided into 4 groups (n=10 each):sham operation group (group Sham),group NP,negative control group (group NC) and group CBP.NP was induced by CCI at 5 days after successful implantation of the intrathecal catheter.Normal saline,negative lentivirus vector (RNAi-NC-LV) and CBP shRNA lentivirus vector (CBP RNAi-LV) 20 μl were injected intrathecally at 7 days after CCI in groups NP,NC and CBP,respectively.Paw withdrawal threshold to mechanical stimuli (MWT)and paw withdrawal latency to thermal stimulus (TWL) were measured at 1 day before operation and at 3,5,7,10,12 and 14 days after operation.The rats were sacrificed after the measurement of MWT and TWL at 14 days after operation and the lumbar segment of the spinal cord was then removed for determination of the expression of CBP,acetylated histone H3/H4 (Ac-H3,Ac-H4) and COX-2 protein (by immunohistochemistry),and CBP and COX-2 mRNA (by RF-PCR).Results Compared with group Sham,MWT and TWL were significantly decreased at different time points after operation in groups NP,NCand CBP,and the expression of CBP,Ac-H3,Ac-H4 and COX-2 protein,and CBP and COX-2 mRNA was up-regulated at 14 days after operation in groups NP and NC (P ＜ 0.05).Compared with group NP,MWT and TWL were significantly increased at 10,12 and 14 days after operation and the expression of CBP,Ac-H3,Ac-H4 and COX-2 protein,and CBP and COX-2 mRNA was downregulated at 14 days after operation in group CBP (P ＜ 0.05).Conclusion CBP is involved in the development of NP by up-regulating COX-2 expression and increasing histone H3 and H4 acetylation in spinal cord.

A novel fluid resuscitation strategy modulates pulmonary transcription factor activation in a murine model of hemorrhagic shock

INTRODUCTION: Combining the hemodynamic and immune benefits of hypertonic saline with the anti-inflammatory effects of the phosphodiesterase inhibitor pentoxifylline (HSPTX) as a hemorrhagic shock resuscitation strategy reduces lung injury when compared with the effects of Ringer's lactate (RL). We hypothesized that HSPTX exerts its anti-inflammatory effects by interfering with nuclear factor kappa B/cAMP response element-binding protein (NF-êB-CREB) competition for the coactivator CREB-binding protein (CBP) in lung tissue, thus affecting pro-inflammatory mediator production. METHODS: Male Sprague-Dawley rats underwent 60 minutes of hemorrhagic shock to reach a mean arterial blood pressure of 35 mmHg followed by resuscitation with either RL or HSPTX (7.5 percent HS + 25 mg/kg PTX). After four hours, lung samples were collected. NF-êB activation was assessed by measuring the levels of phosphorylated cytoplasmic inhibitor of kappa B (I-êB) and nuclear NF-êB p65 by western blot. NF-êB and CREB DNA-binding activity were measured by electrophoretic mobility shift assay (EMSA). Competition between NF-êB and CREB for the coactivator CBP was determined by immunoprecipitation. Interleukin-8 (IL-8) levels in the lung were measured by ELISA. RESULTS: RL resuscitation produced significantly higher levels of lung IL-8 levels, I-êB phosphorylation, p65 phosphorylation, and NF-êB DNA binding compared with HSPTX. NF-êB-CBP-binding activity was similar in both groups, whereas CREB-CBP-binding activity was significantly increased with HSPTX. CREB-DNA binding-activity increased to a greater level with HSPTX compared with RL. DISCUSSION: HSPTX decreases lung inflammation following hemorrhagic shock compared with conventional resuscitation using RL through attenuation of NF-êB signaling and increased CREB-DNA binding activity. HSPTX may have therapeutic potential in the attenuation of ischemia-reperfusion...

A case of Rubinstein-Taybi Syndrome with a CREBbinding protein gene mutation / 소아과

Rubinstein-Taybi syndrome (RTS) is a congenital disorder characterized by typical facial features, broad thumbs and toes, with mental retardation. Additionally, tumors, keloids and various congenital anomalies including congenital heart defects have been reported in RTS patients. In about 50% of the patients, mutations in the CREB binding protein (CREBBP) have been found, which are understood to be associated with cell growth and proliferation. Here, we describe a typical RTS patient with Arnold-Chiari malformation. A mutation in the CREBBP gene, c.4944_4945insC, was identified by mutational analysis.

Effects of memantine hydrochloride on the expressions of cAMP responsive element binding protein and cytochrome c in vascular dementia in rats / 国际脑血管病杂志

Objective To investigate the effects of memantine hydrochloride on the learning and memory function in vascular dementia (VaD) in rats and its possible mechanism.Methods A rat VaD model was induced by using permanent bilateral common carotid artery ligatioa A total of 36 SD rats were randomly divided into sham-operation group, VaD group,and memantine group (memantine hydrochloride was given by intragastric administration, once a day, for eight weeks) (n = 12 in each group). Y maze test was used to observe their behavioral changes. Immunohistochemistry technique was used to detect the changes of the expressions of cAMP responsive element binding protein (CREB) and cytochrome c (CytC) in hippocampal CA1 region and cortex; and TUNEL method was used to detect neuronal apoptosis. Results The learning and memory abilities in memantine group were 50.17 ± 5.56 and 7.08 ± 0.90 respectively, and they were significantly better than 66.36 ± 5.41 and 4.64 ± 1.03 in the VaD group (all P＜0.01); the mean absorbencies of CREB in hippocampal CA1 region and cortex were 147.51 ± 7.11 and 155.37 ± 4.52, respectively, and they were significantly higher than 135.11 ± 8.52 and 142.39 ± 5.24 in the VaD group (all P＜0.01); and the mean absorbencies of CytC in hippocampal CA1 region and cortex were 116.53 ± 4.91 and 113.51 ± 6.05, and they wre significantly lower than 136.65 ±7.43 and 138.09 ±4.88 in the VaD group (all P ＜ 0.01); the extent of apoptosis in the memantine group was also improved significantly compared to the VaD group. Conclusions Memantine hydrochloride may improve the learning and memory function in VaD rats by upregulating the expression of CREB and inhibiting the release of CytC and neuronal apoptosis.