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1.
Fiore Manganelli Silvia Parisi Maria Nolano Francesco Miceli Stefano Tozza Chiara Pisciotta Rosa Iodice Vincenzo Provitera Rita Cicatiello Stephan Zuchner Maurizio Taglialatela Tommaso Russo Lucio Santoro 《Journal of the peripheral nervous system : JPNS》2019,24(4):330-339
The development of patient‐specific induced pluripotent stem cells (iPSCs) offered interesting insights in modeling the pathogenesis of Charcot‐Marie‐Tooth (CMT) disease and thus we decided to explore the phenotypes of iPSCs derived from a single CMT patient carrying a mutant ATP1A1 allele (p.Pro600Ala). iPSCs clones generated from CMT and control fibroblasts, were induced to differentiate into neural precursors and then into post‐mitotic neurons. Control iPSCs differentiated into neuronal precursors and then into post‐mitotic neurons within 6‐8 days. On the contrary, the differentiation of CMT iPSCs was clearly defective. Electrophysiological properties confirmed that post‐mitotic neurons were less mature compared to the normal counterpart. The impairment of in vitro differentiation of CMT iPSCs only concerned with the neuronal pathway, because they were able to differentiate into mesendodermal cells and other ectodermal derivatives. ATP1A1 was undetectable in the few neuronal cells derived from CMT iPSCs. ATP1A1 gene mutation (p.Pro600Ala), responsible for a form of axonal CMT disease, is associated in vitro with a dramatic alteration of the differentiation of patient‐derived iPSCs into post‐mitotic neurons. Thus, the defect in neuronal cell development might lead in vivo to a decreased number of mature neurons in ATP1A1‐CMT disease. 相似文献
2.
目的分析Na+/H+交换蛋白1(NHE1)抑制剂对癌基因BRAF野生型(BRAFWT)和激活型BRAFV600E突变的胶质母细胞瘤(GBM)细胞生长和侵袭能力的影响。
方法NHE1抑制剂Cariporide分别处理U251(BRAFWT)和AM38(BRAFV600E)GBM细胞系,乙酰甲酯化的2’,7’-双(2-羧乙基)-5(6)-羧荧光素荧光探针处理细胞并采用紫外分光光度计检测细胞在440 nm与490 nm的荧光强度,计算荧光强度比值以反映NHE1的活性,MTT法检测细胞增殖活性,基质胶-Transwell实验检测细胞侵袭能力。
结果AM38细胞的NHE1活性、增殖和侵袭能力均显著高于U251细胞,差异均有统计学意义(P=0.006、0.010、0.047);Cariporide处理的U251和AM38细胞的NHE1活性、增殖和侵袭能力均显著低于溶剂二甲基亚砜处理的U251和AM38细胞,差异均有统计学意义(U251:P=0.012、0.023、0.044;AM38:P=0.006、0.001、0.038)。
结论采用Cariporide阻断NHE1活性可有效抑制BRAFWT和BRAFV600E突变型GBM细胞的增殖和侵袭。 相似文献
3.
Emilio Domínguez‐Salazar Gabriela Hurtado‐Alvarado Fernanda Medina‐Flores Javik Dorantes Oscar Gonzlez‐Flores Arturo Contis‐Montes de Oca Javier Velzquez‐Moctezuma Beatriz Gmez‐Gonzlez 《Journal of sleep research》2020,29(3)
Sleep loss increases blood–brain barrier permeability. As the blood–brain barrier and the blood–tissue barriers in the reproductive tract (blood–testis and blood–epididymis barriers) share common characteristics, we hypothesized that sleep restriction may also modify their barrier function. Previous reports showed that sleep loss decreased sperm viability and progressive fast mobility, which may be a consequence of altered blood–testis and blood–epididymis barrier. Therefore, we quantified changes in blood–testis and blood–epididymis barrier after sleep loss and related them to male fertility. Adult male Wistar rats were sleep restricted using the multiple‐platform technique in a protocol of 20 hr daily sleep deprivation plus 4 hr of sleep recovery in the home‐cage. At the 10th day, barrier permeability assays were performed with Na‐fluorescein, 10 kDa Cascade blue‐dextrans and Evans blue, and the expression of tight junction proteins, actin and androgen receptor was quantified. At the 10th day of sleep restriction and after sleep recovery days 1–7, males were placed with sexually receptive females, sexual behaviour was tested, and the percentage of pregnancies was calculated. Sleep restriction increased the barrier permeability to low‐ and high‐molecular‐weight tracers, and decreased the expression of tight junction proteins, actin and androgen receptor. Concomitantly, sleep restriction reduced the percentage of ejaculating males and the number of pregnancies. Sleep recovery for 2–3 days progressively re‐established fertility, as indicated by a higher percentage of ejaculating males and impregnated females. In conclusion, chronic sleep loss alters fertility concomitantly with the disruption of the blood–tissue barriers at the reproductive tract, the mechanism involves androgen signalling. 相似文献
4.
5.
Gitelman综合征是由位于染色体16q13的SLC12A3基因突变引起的常染色体隐性遗传病,患病率为1~10∶40000,SLC12A3基因编码噻嗪类敏感的钠氯共同转运体(sodium-chloride cotransporters,NCC),介导Na+和Cl-的重吸收。该综合征以低钾性碱中毒、低镁血症和低尿钙为特征,基因型与表型之间有一定的相关性。在之前的研究中,已经发现了超过500种基因突变,并对其中的一些突变进行了功能学分析。本文综述了Gitelman综合征相关的基因突变和功能学研究,对其基因型和表型的关系进行了分析,总结了Gitelman综合征的分子遗传学研究进展。 相似文献
6.
Activation of voltage‐gated sodium current and inhibition of erg‐mediated potassium current caused by telmisartan,an antagonist of angiotensin II type‐1 receptor,in HL‐1 atrial cardiomyocytes 下载免费PDF全文
Telmisartan (TEL) is a non‐peptide blocker of angiotensin II type‐1 (AT1) receptor. However, the mechanisms through which this drug interacts directly with ion currents in hearts remain largely unclear. Herein, we aim to investigate the effects of TEL the on ionic currents and membrane potential of murine HL‐1 cardiomyocytes. In whole‐cell recordings, addition of TEL stimulated the peak and late components of voltage‐gated Na+ currents (INa) with different potencies. The EC50 values required to achieve the stimulatory effect of this drug on peak and late INa were 0.2 and 1.2 μmol/L, respectively, and the current‐voltage relationship of peak INa shifted toward less‐depolarized potentials during exposure to TEL. Telmisartan not only increased peak INa but also prolonged the inactivation time course of late INa. Amiodarone (Amio) or ranolazine (Ran), but not angiotensin II, could reverse TEL‐mediated effects. The drug enhanced the recovery rate of INa inactivation and exerted an inhibitory effect on erg‐mediated K+ and L‐type Ca2+ currents. In whole‐cell current‐clamp recordings, addition of the drug resulted in prolongation of the duration of action potentials (APs) in a dose‐dependent manner in HL‐1 cells; Amio or Ran could reverse this increase in AP durations. Telmisartan‐mediated prolongation of AP was attenuated in KCNH2 siRNA‐transfected HL‐1 cells. In cultured smooth muscle cells of the human coronary artery, TEL enhanced INa amplitudes and slowed current inactivation. Stimulation by TEL of INa in HL‐1 cells did not simply increase current magnitude but altered current kinetics, thereby suggesting state‐dependent activation. Telmisartan may have greater affinity to the open/inactivated state than to the resting state residing in NaV channels. Collectively, TEL‐mediated stimulation of INa and inhibition of IK(erg) could be an important ionic mechanism underlying the increased cell excitability of HL‐1 cells; these actions, however, cannot be entirely explained by its blockade of AT1 receptor. 相似文献
7.
Gas transport concepts in vertebrates have naturally been formulated based on human blood. However, the first vertebrates were aquatic, and fish and tetrapods diverged hundreds of millions years ago. Water‐breathing vertebrates live in an environment with low and variable O2 levels, making environmental O2 an important evolutionary selection pressure in fishes, and various features of their gas transport differ from humans. Erythrocyte function in fish is of current interest, because current environmental changes affect gas transport, and because especially zebrafish is used as a model in biomedical studies, making it important to understand the differences in gas transport between fish and mammals to be able to carry out meaningful studies. Of the close to thirty thousand fish species, teleosts are the most species‐numerous group. However, two additional radiations are discussed: agnathans and elasmobranchs. The gas transport by elasmobranchs may be closest to the ancestors of tetrapods. The major difference in their haemoglobin (Hb) function to humans is their high urea tolerance. Agnathans differ from other vertebrates by having Hbs, where cooperativity is achieved by monomer‐oligomer equilibria. Their erythrocytes also lack the anion exchange pathway with profound effects on CO2 transport. Teleosts are characterized by highly pH sensitive Hbs, which can fail to become fully O2‐saturated at low pH. An adrenergically stimulated Na+/H+ exchanger has evolved in their erythrocyte membrane, and plasma‐accessible carbonic anhydrase can be differentially distributed among their tissues. Together, and differing from other vertebrates, these features can maximize O2 unloading in muscle while ensuring O2 loading in gills. 相似文献
8.
Dynamics of Sodium Ions and Water in Swollen Superabsorbent Hydrogels as Studied by 23Na‐ and 1H‐NMR
Xiaoai Guo Solveig Theissen Jan Claussen Viet Hildebrand Juliane Kamphus Manfred Wilhelm Burkhard Luy Gisela Guthausen 《Macromolecular chemistry and physics.》2019,220(2)
Dynamics of sodium ions and water in swollen superabsorbent polymer (SAP) hydrogels are studied by 23Na‐ and 1H‐NMR, respectively. The apparent diffusion coefficients of water in swollen SAPs, probed by 1H pulsed field gradient NMR, decreases with increasing diffusion time. The degree of hindrance depends on structural and synthesis parameters. It is quantified within a tortuosity model. Based on the results, the swelling degree has the highest impact on the ion mobility, apart from synthesis parameters leading to different levels of physical and chemical crosslinks. 23Na‐NMR relaxation and diffusion reveal the 23Na+ mobility in swollen SAPs. A higher degree of neutralization leads to faster relaxation and to a smaller apparent diffusion coefficient. Surface crosslinking restricts water mobility, but has a smaller impact on the dynamics of sodium ions. The experimental results indicate an influence of SAP structure on the dynamics of ions and water molecules. 相似文献
9.
We examined the expression of Na(+)/K(+)-ATPase alpha-subunit isoforms in rat salivary glands by RT-PCR. Isoform alpha1 was expressed strongly in all three major salivary glands. The alpha2 isoform was expressed in both submandibular gland (SMG) and sublingual gland (SLG) but faintly in the parotid gland (PG). The alpha3 was detected only in the SLG, and the alpha3 mRNA in the SLG was 1/8 of its level in the brain. Na(+)/K(+)-ATPase alpha3 isoform in the SLG, was localized predominantly on the basolateral plasma membranes in serous cells by immunohistochemical method. We also found the presence of natural antisense RNA of the alpha3 isoform in rat SLG: the 1st-strand cDNA prepared with gene-specific forward primers targeted to the CDS region and to the promoter region of the alpha3 gene in place of oligo(dT) or gene-specific reverse primers produced reasonable PCR products corresponding to the alpha3 cDNA sequence by the subsequent PCR reaction. Synthesis of the 1st-strand cDNA with the gene-specific forward primers was prevented by RNase digestion of the total RNA preparation, indicating that the PCR products in the RT-PCR system were not due to the contaminated genomic DNA, if any. The alpha3 protein level in rat SLG increased with aging, and levels of both alpha3 mRNA (sense RNA) and alpha3 antisense RNA were higher in SLGs of aged rats than in those of young rats, respectively. 相似文献
10.
变形链球菌耐氟菌株与亲代菌株质子移位膜ATP酶活性的比较 总被引:1,自引:0,他引:1
目的:通过测定并比较变形链球菌耐氟菌株及其亲代菌株体内质子移位膜ATP酶的活性,以阐明耐氟菌株耐酸能力提高的原因。方法:将变链菌株Ingbritt及其耐氟突变株Ingbritt-FR通过甲苯处理,2个循环的液氮冷冻和37℃解冻,制成透性细胞。将透性细胞悬液加到含有10mmol/LMgSO4的50mmol/LTris-maleate测试缓冲液中(pH6.0),加温至37℃,再加入5mmol/LATP(pH6.0)起动反应。分别于10、20、60min取样,测定样品中水解ATP所释出的无机磷量。采用磷钼酸比色法在紫外分光光度计上进行比色分析(660nm),所得数据采用双因素方差分析。结果:在10、20和60min时,耐氟菌株H+-ATP酶活性分别为308.48、136.67和82.80μmolPi/g细胞干重/min,显著高于亲代菌株的相应酶活性:104.77,、64.69和30.70(P<0.01)。随时间推移,两类菌株的H+-ATP酶活性均逐渐降低,在酶的作用时间差别上有统计学意义(P<0.01)。结论:耐氟菌株ATP酶活性增高为其耐酸性增高的原因;H+-ATP酶活性及耐酸性的增高将会增加变链菌耐氟菌株的致龋潜能。 相似文献