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991.
N-acetylglucosaminyltransferase V (GnT-V) is an important tumorigenesis and metastasis-associated enzyme. To study its biofunction, the GnT-V stably suppressed cell line (GnT-V-AS/7721) was constructed from 7721 hepatocarcinoma cells in previous study. In this study, cDNA array gene expression profiles were compared between GnT-V-AS/7721 and parental 7721 cells. The data indicated that GnT-V-AS/7721 showed a characteristic expression pattern consistent with the ER stress. The molecular mechanism of the ER stress was explored in GnT-V-AS/7721 by the analysis on key molecules in both two unfolded protein response (UPR) pathways. For ATF6 and Irel/XBP-1 pathway, it was evidenced by the up-regulation of BIP at mRNA and protein level, and the appearance of the spliced form ofXBP-1. As for PERK/eIF2α pathway, the activation of ER eIF2α kinase PERK was observed. To confirm the results from GriT-V-AS/7721 cells, the key molecules in the UPR were examined again in 7721 cells interfered with the GnT-V by the specific RNAi treatment. The results were similar with those from GnT-V-AS/7721, indicating that blocking of GnT-V can specifically activate ER stress in 7721 cells. Rate of 3H-Man incorporation corrected with rate of 3H-Leu incorporation in GnT-V-AS/7721 was down-regulated greatly compared with the control, which demonstrated the deficient function of the enzyme synthesizing N-glycans after GnT-V blocking. Moreover, the faster migrating form of chaperone GRP94 associated with the underglycosylation, and the extensively changed N-glycans structures of intracellular glycoproteins were also detected in GnT-V-AS/7721. These results supported the mechanism that blocking of GnT-V expression impaired functions of chaperones and N-glycan-synthesizing enzymes, which caused UPR in vivo. 相似文献
992.
Ju Yuan Bao-Zeng Xu Shu-Tao Qi Jing-Shan Tong Liang Wei Mo Li Ying-Chun Ouyang Yi Hou Heide Schatten Qing-Yuan Sun 《PloS one》2010,5(6)
MAPK-activated protein kinase 2 (MK2), a direct substrate of p38 MAPK, plays key roles in multiple physiological functions in mitosis. Here, we show for the first time the unique distribution pattern of MK2 in meiosis. Phospho-MK2 was localized on bipolar spindle minus ends and along the interstitial axes of homologous chromosomes extending over centromere regions and arm regions at metaphase of first meiosis (MI stage) in mouse oocytes. At metaphase of second meiosis (MII stage), p-MK2 was localized on the bipolar spindle minus ends and at the inner centromere region of sister chromatids as dots. Knockdown or inhibition of MK2 resulted in spindle defects. Spindles were surrounded by irregular nondisjunction chromosomes, which were arranged in an amphitelic or syntelic/monotelic manner, or chromosomes detached from the spindles. Kinetochore–microtubule attachments were impaired in MK2-deficient oocytes because spindle microtubules became unstable in response to cold treatment. In addition, homologous chromosome segregation and meiosis progression were inhibited in these oocytes. Our data suggest that MK2 may be essential for functional meiotic bipolar spindle formation, chromosome segregation and proper kinetochore–microtubule attachments. 相似文献
993.
994.
Fusheng Liu Hou Wu Xiaoyu Yang Yuqin Dong Guoyou Huang Guy M. Genin Tian Jian Lu Feng Xu 《Biophysical journal》2021,120(17):3764-3775
Although coupling between cardiomyocytes and myofibroblasts is well known to affect the physiology and pathophysiology of cardiac tissues across species, relating these observations to humans is challenging because the effect of this coupling varies across species and because the sources of these effects are not known. To identify the sources of cross-species variation, we built upon previous mathematical models of myofibroblast electrophysiology and developed a mechanoelectrical model of cardiomyocyte-myofibroblast interactions as mediated by electrotonic coupling and transforming growth factor-β1. The model, as verified by experimental data from the literature, predicted that both electrotonic coupling and transforming growth factor-β1 interaction between myocytes and myofibroblast prolonged action potential in rat myocytes but shortened action potential in human myocytes. This variance could be explained by differences in the transient outward K+ current associated with differential Kv4.2 gene expression across species. Results are useful for efforts to extrapolate the results of animal models to the predicted effects in humans and point to potential therapeutic targets for fibrotic cardiomyopathy. 相似文献
995.
JinLan Huang Fan Zhang Min Su Jiaxin Li Wen Yi LiXiang Hou SiMan Yang JinYuan Liu HaoAn Zhang Tengfei Ma DengPan Wu 《Aging cell》2021,20(9)
Age‐related cognitive decline in neurodegenerative diseases, such as Alzheimer''s disease (AD), is associated with the deficits of synaptic plasticity. Therefore, exploring promising targets to enhance synaptic plasticity in neurodegenerative disorders is crucial. It has been demonstrated that methyl‐CpG binding protein 2 (MeCP2) plays a vital role in neuronal development and MeCP2 malfunction causes various neurodevelopmental disorders. However, the role of MeCP2 in neurodegenerative diseases has been less reported. In the study, we found that MeCP2 expression in the hippocampus was reduced in the hippocampus of senescence‐accelerated mice P8 (SAMP8) mice. Overexpression of hippocampal MeCP2 could elevate synaptic plasticity and cognitive function in SAMP8 mice, while knockdown of MeCP2 impaired synaptic plasticity and cognitive function in senescence accelerated‐resistant 1 (SAMR1) mice. MeCP2‐mediated regulation of synaptic plasticity may be associated with CREB1 pathway. These results suggest that MeCP2 plays a vital role in age‐related cognitive decline by regulating synaptic plasticity and indicate that MeCP2 may be promising targets for the treatment of age‐related cognitive decline in neurodegenerative diseases. 相似文献
996.
Zhimin Liu Wenkai Shou Jianqiang Qian Jing Wu Carlos Alberto Busso Xianzhang Hou 《Journal of Plant Ecology》2018,11(6):866
Aims
This study aimed to examine the changes in plant species richness, frequency and density along a habitat fragmentation gradient (with varied degrees of habitat fragmentation [DHFs]) in a desertified grassland of Horqin Sandy Land, northeastern Inner Mongolia, China. 相似文献
997.
目的探讨人脐带间充质干细胞(MSCs)源性细胞外囊泡Oct-4 mRNA对受损的肾小管上皮细胞修复的作用及相关机制。
方法将培养的缺氧损伤肾小管上皮细胞置于含有人脐带MSCs细胞外囊泡及不同对照培养液的培养腔室玻片上孵育48?h,应用BrdU及TUNEL染色,检测各组细胞增殖或凋亡情况。将急性肾损伤模型小鼠分为4组:空白组、EVs组、Oct-4过表达组、Oct-4低敲组。并按照分组分别注射磷酸盐缓冲液(Vehicle),人脐带MSCs细胞外囊泡(EVs),过表达Oct-4基因的人脐带MSCs细胞外囊泡(EVs?+?Oct-4)及敲除Oct-4基因的人脐带MSCs外囊泡(EVs-Oct-4),并在注射48?h及2周后采血测肌酐(Crea)及尿素氮(BUN),了解肾功能变化;对各组上述处理后的肾组织应用TUNEL与增殖细胞核抗原表达量检测各组肾脏细胞凋亡与增殖情况;通过Masson染色检测了各组肾脏纤维化程度;通过PCR探索肾损伤后肾组织细胞Snail基因的表达变化。数据分析采用方差分析和SNK-q检验。
结果EVs?+ Oct-4处理缺氧的肾小管上皮细胞48?h后,TUNEL染色显示具有最少的凋亡细胞数(0~1)/?HPF,BrdU显示有最多的增殖细胞(7±2)/HPF。EVs,EV-Oct-4以及Vehicle对体外缺氧肾小管上皮细胞的上述作用依次减弱(P?0.01)。急性肾损伤后,注射EVs?+?Oct-4可降低肾损伤后Crea水平(28?mmol/L)和BUN水平(17?mmol/L);并抑制肾组织纤维化,使Masson染色阳性面积减少至(3.2±1.0)﹪;同时提高肾组织PCNA染色阳性细胞数(损伤48h后为(70±7)/HPF,2周后为(21±4)/HPF,减少TUNEL染色阳性细胞数[损伤48?h后为(2±1)/HPF,2周后为(3±2)/?HPF]。注射EVs,EV-Oct-4以及Vehicle对产生上述效应的作用依次减弱(P?0.01)。PCR结果表明,Vehicle组肾小管上皮细胞Snail表达最高2.3±0.2,而EVs + Oct-4则可降低Snail表达0.7±0.1。
结论EVs可通过抑制凋亡促进增殖、抑制纤维化治疗肾损伤,而这其中EVs包含的OCT-4 mRNA可通过抑制肾损伤后Snail基因的表达来抑制肾脏纤维化的形成。 相似文献
998.
999.
Formation of the IGF1R/CAV1/SRC tri‐complex antagonizes TRAIL‐induced apoptosis in gastric cancer cells 下载免费PDF全文
1000.