作者机构：
[Li, Wenjuan; Zhang, Zuping; Li, Xiaoling; Wang, Wei; Ma, Jian; Xiong, Wei; Wu, Minghua; Liao, Qianjin; Xiang, Bo; Li, Guiyuan; Yi, Mei] Cent S Univ, Xiangya Sch Med, Canc Res Inst, Changsha 410078, Hunan, Peoples R China.;[Li, Xiayu] Cent S Univ, Xiangya Hosp 3, Dept Gastroenterol, Changsha 410013, Hunan, Peoples R China.;[Tan, Yixin] Cent S Univ, Xiangya Hosp 2, Dept Dermatol, Changsha 410008, Hunan, Peoples R China.;[Yi, Mei] Cent S Univ, Xiangya Hosp, Dept Dermatol, Changsha 410008, Hunan, Peoples R China.;[McCarthy, James B.; Yang, Jianbo] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
通讯机构：
[Xiang, Bo] C;Cent S Univ, Xiangya Sch Med, Canc Res Inst, Xiangya Rd, Changsha 410078, Hunan, Peoples R China.
摘要：
Promoter hypermethylation-mediated silencing of tumor suppressor genes (TSGs) is a hallmark of oncogenesis. Oxidored-nitro domain-containing protein 1 (NOR1) is a candidate TSG that is downregulated in nasopharyngeal carcinoma (NPC). In the present study, we identified a functional NOR1 promoter that is regulated by heat shock factor 1 and nuclear respiratory factor 1. The promoter is located within a CpG island. Hypermethylation of this CpG island was found in NPC tissue samples and cancer cell lines, whereas no aberrant promoter methylation was detected in non-cancerous nasopharyngeal tissue samples or normal nasopharyngeal epithelial cells. Treatment of NPC 6-10B cells and leukemia HL60 cells with 5′-aza-2′-deoxycytidine increased endogenous levels of NOR1 messenger RNA. Ectopic expression of NOR1 in NPC HNE1 cells inhibited tumor cell colony formation and viability. These findings suggest that promoter hypermethylation may participate in transcriptional inactivation of the NOR1 gene in NPC. Frequent epigenetic inactivation of the NOR1 gene in NPC suggests that it may be a critical tumor suppressor involved in the development of NPC.
作者机构：
[李凯; 郭紫芬; 冯勇; 廖端芳] Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, Hunan Province, China;Guo Zi-FenSymbol, Doctor, Associate professor, Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, Hunan Province, China;Vascular smooth muscle cells grow well in culture condition using static hydrostatic pressure instead of serum.;To investigate the effect of continuous static hydrostatic pressure on the proliferation of vascular smooth muscle cells.;Vascular smooth muscle cell A10 and vascular endothelial cell HUVEC-12 were cultured in a self-developed pressure adjustable incubator, under different pressures of 0, 12, 16, 20, 24 and 28 kPa respectively.
通讯机构：
[Liao, D.-f.] I;Institute of Pharmacy and Pharmacology, , Hengyang 421001, Hunan Province, China
摘要：
Previously, we found that G protein-coupled receptor APJ endogenous ligand apelin-13 stimulates vascular smooth muscle cells (VSMC) proliferation mediated in part by PKC-PI3K-ERK1/2-cyclinDl signaling cascades. In this study, Raf-1-14-3-3 signaling in rat VSMCs proliferation stimulated by apelin-13 was further investigated. Cell proliferation was measured with MTT assay. Expression of PI3K, phospho-PI3K, Raf-1, phospho-Raf-1, ERK1/2, phospho-ERKl/2, cyclinDl and cyclinE were detected by Western blotting. 14-3-3 protein combining with Raf-1 was detected by immunoprecipitation. Here, we demonstrated that apelin-13 increased the expression of 14-3-3, Raf-1 phosphorylation and ERK1/2 phosphorylation in a concentration- dependent and time-dependent manner at 0~4 μmol/L and 0~48 h. 14-3-3 inhibitor Difopein decreased the apelin-13-induced Raf-1 phosphorylation, ERK1/2 phosphorylation, expression of cyclinDl and cyclinE. Furthermore, apelin-13 promoted the combination of 14-3-3 protein and Raf-1, Difopein significantly inhibited the combination of 14-3-3 and Raf-1 stimulated by apelin-13. Similarly, Difopein significantly inhibited the VSMCs proliferation stimulated by apelin-13. Our results revealed that Raf-1 +14-3-3-ERK1/2 signaling cascades mediated the effect of apelin-13 on rat VSMCs proliferation.
作者机构：
[Xiao, Guohua; Wang, Zongbao; Yu, Jian; Zhang, Yali; Zhang, Sujun; Yin, Weidong; Wang, Yueting] Univ S China, Inst Biochem & Mol Biol, Hengyang 421001, Peoples R China.;[Wang, Zongbao] Univ S China, Dept Lab Anim Sci, Hengyang 421001, Peoples R China.;[Zeng, Huaicai] Univ S China, Sch Publ Hlth, Hengyang 421001, Peoples R China.
通讯机构：
[Wang, Zongbao] U;Univ S China, Inst Biochem & Mol Biol, Hengyang 421001, Peoples R China.
摘要：
Objective: Endothelial dysfunction is a key event in the onset and progression of atherosclerosis associated with diabetes. Increasing cell apoptosis may lead to endothelial dysfunction and contribute to vascular complications. Therefore, we aimed to elucidate the possible role and mechanism of ibrolipim in preventing endothelial dysfunction induced by high glucose. Methods: Human umbilical vein endothelial cells (HUVECs) were cultured respectively under normal glucose level (5.5 mM), high glucose level (33 mM), and high glucose level with ibrolipim treatment. Endothelial dysfunction was identified by the expression of ET-1 and vWF through reverse transcription PCR (RT-PCR). HUVECs apoptosis was assessed by fluorescent staining with Hoechst 33258. Akt activity was analyzed by western blot. Results: High glucose condition significantly increased the rate of apoptotic cells, weakened cell viability, and decreased the expression of ET-1 and vWF. Ibrolipim treatment significantly attenuated these alterations of endothelial dysfunction. The lower concentrations (2, 4, 8 μM) of ibrolipim inhibited apoptosis of cultured HUVECs, improved cell viability, down-regulated the mRNA levels of ET-1, vWF, and attenuated the cytotoxicity; however, higher concentration (16, 32 μM) of ibrolipim aggravated the damage of HUVECs cultured under high glucose level. Meanwhile, high glucose induced a decrease of Akt activity which led to apoptosis, and ibrolipim prevented the decrease and attenuated apoptotic effect induced by high glucose. Furthermore, the PI3K inhibitor LY294002 significantly abolished the anti-apoptotic effect of ibrolipim, and decreased Akt phosphorylation. Although, the expression of Akt mRNA and total protein were not altered in cultured HUVECs. Conclusion: Ibrolipim at lower concentrations can inhibit high glucose-induced apoptosis in cultured HUVECs, which might be related to the alternation of Akt activity. Ibrolipim has the potential to attenuate endothelial dysfunction and lower the risk of diabetes-associated vascular diseases. And it might be a therapeutic agent for diabetic vascular complications.
摘要：
The role of renal lipoprotein lipase (LPL) per se in kidney diseases is still controversial and obscure. The purpose of this study was to observe the preventive effects of Ibrolipim, a LPL activator, on lipid accumulation and LPL expression in the kidneys of minipigs fed a high-sucrose and high-fat diet (HSFD). Male Chinese Bama minipigs were fed a control diet or HSFD with or without 0.1 g/kg/day Ibrolipim for 5 months. Body weight, plasma glucose, insulin, lipids, LPL activity, and urinary microalbumin were measured. Renal tissue was obtained for detecting LPL activity and contents of triglyceride and cholesterol, observing the renal lipid accumulation by Oil Red O staining, and examining the mRNA and protein expression of LPL by real time PCR, Western Blot and immunohistochemistry. Feeding HSFD to minipigs caused weight gain, hyperglycemia, hyperinsulinemia, hyperlipidemia and microalbuminuria. HSFD increased plasma LPL activity while it decreased the mRNA and protein expression and activity of LPL in the kidney. The increases in renal triglyceride and cholesterol contents were associated with the decrease in renal LPL activity of HSFD-fed minipigs. In contrast, supplementing Ibrolipim into HSFD lowered body weight, plasma glucose, insulin, triglyceride and urinary albumin concentrations while it increased plasma total cholesterol and HDL-C. Ibrolipim suppressed the renal accumulation of triglyceride and cholesterol, and stimulated the diet-induced down-regulation of LPL expression and activity in the kidney. Ibrolipim exerts renoprotective and hypolipidemic effects via the increase in renal LPL activity and expression, and thus the increased expression and activity of renal LPL play a vital role in suppressing renal lipid accumulation and ameliorating proteinuria in diet-induced diabetic minipigs.
摘要：
Fragile X-related protein 1（FXR1P） is a member of the FXR gene family,which also includes fragile X mental retardation protein and fragile X-related protein 2（FXR2P）.To understand the functions of FXR1P,we screened FXR1P-interacting proteins using a yeast two-hybrid system.FXR1P was fused to pGBKT7 and used as the bait to screen a human fetal brain cDNA library.This screening revealed 10 FXR1P-interacting proteins including FTH1.FTH1 encodes Homo sapiens ferritin,heavy polypeptide 1.The interaction between FXR1P and FTH1 was confirmed by retesting in yeast using both a β-galactosidase assay and growth studies on selective media.A co-immunoprecipitation assay in mammalian cells further confirmed the FXR1P/FTH1 interaction.Moreover,the results revealed that FTH1 colocalized with FXR1P in the cytoplasm around the nucleus in mammalian cells.The present findings suggest that FXR1P plays an important role in iron metabolism in the brain by interacting with FTH1.This provides clues for elucidating the relationship between FXR1P function and fragile X syndrome.
作者机构：
[Ouyang, X.; Zhou, S.; Huang, F.; Tian, S.; Gao, J.; Yan, Y.; Deng, H.] Univ S China, Dept Physiol, Coll Med, Hengyang 421001, Hunan, Peoples R China.;[Li, P.] Univ S China, Dept Biol, Coll Life Sci & Technol, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Tian, S.] U;Univ S China, Dept Physiol, Coll Med, Hengyang 421001, Hunan, Peoples R China.
关键词：
Fear conditioning;Fear extinction;Learning;Memory;Ventrolateral prefrontal cortex;Ventromedial prefrontal cortex
摘要：
Recent evidence has demonstrated that the ventromedial prefrontal cortex (vmPFC) is a critical site of the neural circuits underlying fear extinction memory. The ventrolateral prefrontal cortex (vlPFC) is not directly involved in extinction processes within the aversive domain. However, most of the current cumulated data on extinction is based on a classical delay fear conditioning paradigm in which the interval between the onset of the conditioned stimulus (CS) and the unconditioned stimulus (US) is consistent in a given protocol. In the present study, we developed a modified delay fear conditioning paradigm in which the temporal distribution of the footshock US during the duration of the tone CS is programmed to be pseudorandom. Here, we examined the effects of electrolytic vmPFC and vlPFC lesions made before training on conditioned fear response in the modified paradigm. The behavioral procedure involved four sessions with a 24-h interval: habituation, fear conditioning, extinction training, and extinction test. Percent freezing to tone was assessed as a measure of conditioned fear response. The results show that neither vmPFC nor vlPFC lesions affect acquisition or extinction of conditioned fear response during the fear conditioning and extinction training sessions, respectively. During the extinction test session, both vmPFC- and vlPFC-lesioned rats showed deficits in the recall of the between-session extinction memory. The deficits could not be attributed to altered nonspecific responses (footshock sensitivity, locomotor activity, and nonspecific freezing response). Furthermore, vlPFC lesions made before training had no effect on conditioned fear response in the classical fear conditioning paradigm. These data suggest a preserved role of the vmPFC in fear extinction and a selective involvement of the vlPFC in extinction process in certain fear conditioning tasks.
