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排序方式: 共有426条查询结果,搜索用时 15 毫秒
421.
Riihonen R Supuran CT Parkkila S Pastorekova S Väänänen HK Laitala-Leinonen T 《BONE》2007,40(4):1021-1031
Osteoclasts are multinucleated bone-resorbing cells that use multiple pH regulation mechanisms to create an acidic pH in the resorption lacuna. Carbonic anhydrase II and vacuolar H(+)-ATPases produce and transport protons, while chloride channels provide a Cl(-) flux into the resorption site. These activities are required for inorganic matrix dissolution that precedes enzymatic removal of organic bone matrix. In other cell types it has become evident that carbonic anhydrase isoenzymes interact with AE proteins to form transport metabolons that regulate intracellular pH. Membrane-bound carbonic anhydrase isoenzymes may also compensate for the lack of cytoplasmic carbonic anhydrase II. Therefore, our goal was to explore the expression of membrane-bound carbonic anhydrase (CA) isoenzymes CA IV, CA IX, CA XII and CA XIV in bone-resorbing osteoclasts. Immunohistochemistry and confocal microscopy showed expression of CA IV, CA XII and CA XIV in cultured rat and human osteoclasts. To confirm these results, RT-PCR was used. Immunohistochemistry revealed distinct staining patterns for CA IV, CA XII and CA XIV in rat trabecular bone specimens. A plasma membrane staining was observed in bone lining cells with the CA XII antibody while osteoclast plasma membranes were stained with CA IV and CA XIV antibodies. Confocal microscopy of cultured human osteoclasts showed a punctated intracellular CA IV staining and a perinuclear CA XIV staining while no CA IX or CA XII staining was observed. To evaluate the physiological role of membrane-bound CAs in osteoclasts, we used PCS, a novel membrane-impermeable CA inhibitor. Increased osteoclast number and bone resorption activity was observed in rat osteoclast cultures exposed to a low concentration of PCS while higher concentrations affected cell survival. PCS treatment also disturbed intracellular acidification in osteoclasts, as determined by live cell microscopy. In conclusion, our data shows that membrane-bound carbonic anhydrase isoenzymes CA IV and CA XIV are expressed both at mRNA and protein levels in osteoclasts in vivo and in vitro. In addition, the inhibitor experiments provide novel evidence to support the hypothesis that intracellular pH regulation in osteoclasts may indeed involve transport metabolons. 相似文献
422.
Möttönen R Calvert GA Jääskeläinen IP Matthews PM Thesen T Tuomainen J Sams M 《NeuroImage》2006,30(2):563-569
The left superior temporal cortex shows greater responsiveness to speech than to non-speech sounds according to previous neuroimaging studies, suggesting that this brain region has a special role in speech processing. However, since speech sounds differ acoustically from the non-speech sounds, it is possible that this region is not involved in speech perception per se, but rather in processing of some complex acoustic features. "Sine wave speech" (SWS) provides a tool to study neural speech specificity using identical acoustic stimuli, which can be perceived either as speech or non-speech, depending on previous experience of the stimuli. We scanned 21 subjects using 3T functional MRI in two sessions, both including SWS and control stimuli. In the pre-training session, all subjects perceived the SWS stimuli as non-speech. In the post-training session, the identical stimuli were perceived as speech by 16 subjects. In these subjects, SWS stimuli elicited significantly stronger activity within the left posterior superior temporal sulcus (STSp) in the post- vs. pre-training session. In contrast, activity in this region was not enhanced after training in 5 subjects who did not perceive SWS stimuli as speech. Moreover, the control stimuli, which were always perceived as non-speech, elicited similar activity in this region in both sessions. Altogether, the present findings suggest that activation of the neural speech representations in the left STSp might be a pre-requisite for hearing sounds as speech. 相似文献
423.
424.
Rinnankoski-Tuikka R Silvennoinen M Torvinen S Hulmi JJ Lehti M Kivelä R Reunanen H Kainulainen H 《Nutrition & metabolism》2012,9(1):53-13
Background
The expression of PDK4 is elevated by diabetes, fasting and other conditions associated with the switch from the utilization of glucose to fatty acids as an energy source. It is previously shown that peroxisome proliferator-activated receptor ?? coactivator 1?? (PGC-1??), a master regulator of energy metabolism, coactivates in cell lines pyruvate dehydrogenase kinase-4 (PDK4) gene expression via the estrogen-related receptor ?? (ERR??). We investigated the effects of long-term high-fat diet and physical activity on the expression of PDK4, PGC-1?? and ERR?? and the amount and function of mitochondria in skeletal muscle.Methods
Insulin resistance was induced by a high-fat (HF) diet for 19?weeks in C57BL/6?J mice, which were either sedentary or with access to running wheels. The skeletal muscle expression levels of PDK4, PGC-1?? and ERR?? were measured and the quality and quantity of mitochondrial function was assessed.Results
The HF mice were more insulin-resistant than the low-fat (LF) -fed mice. Upregulation of PDK4 and ERR?? mRNA and protein levels were seen after the HF diet, and when combined with running even more profound effects on the mRNA expression levels were observed. Chronic HF feeding and voluntary running did not have significant effects on PGC-1?? mRNA or protein levels. No remarkable difference was found in the amount or function of mitochondria.Conclusions
Our results support the view that insulin resistance is not mediated by the decreased qualitative or quantitative properties of mitochondria. Instead, the role of PDK4 should be contemplated as a possible contributor to high-fat diet-induced insulin resistance. 相似文献425.
Nuno Maia Nekane Ibarluzea Mala Misra-Isrie Daniel C. Koboldt Isabel Marques Gabriela Soares Rosário Santos Carlo L. M. Marcelis Riikka Keski-Filppula Miriam Guitart Elisabeth Gabau Vila April Lehman Scott Hickey Mari Mori Paulien Terhal Irene Valenzuela Amaia Lasa-Aranzasti Anna Maria Cueto-González Brian H. Chhouk Rebecca C. Yeh Jennifer E. Neil Bassam Abu-Libde Tjitske Kleefstra Mariet W. Elting Andrea Császár Judit Kárteszi Beáta Bessenyei Hans van Bokhoven Paula Jorge Johanna M. van Hagen Arjan P. M. de Brouwer 《American journal of medical genetics. Part A》2023,191(1):135-143
We describe the phenotype of 22 male patients (20 probands) carrying a hemizygous missense variant in MED12. The phenotypic spectrum is very broad ranging from nonspecific intellectual disability (ID) to the three well-known syndromes: Opitz–Kaveggia syndrome, Lujan–Fryns syndrome, or Ohdo syndrome. The identified variants were randomly distributed throughout the gene (p = 0.993, χ2 test), but mostly outside the functional domains (p = 0.004; χ2 test). Statistical analyses did not show a correlation between the MED12-related phenotypes and the locations of the variants (p = 0.295; Pearson correlation), nor the protein domain involved (p = 0.422; Pearson correlation). In conclusion, establishing a genotype–phenotype correlation in MED12-related diseases remains challenging. Therefore, we think that patients with a causative MED12 variant are currently underdiagnosed due to the broad patients' clinical presentations. 相似文献
426.