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41.
Tomaskova Z Gaburjakova J Brezova A Gaburjakova M 《Journal of bioenergetics and biomembranes》2007,39(4):301-311
The objective of this work was to characterize in more detail the inhibition effect of diisothiocyanatostilbene-2′,2-disulfonic
acid (DIDS) on anion channels isolated from the rat heart mitochondria. The channels reconstituted into a planar lipid membrane
displayed limited powers of discrimination between anions and cations and the ion conductance measured under asymmetric (250/50 mM
KCl, cis/trans) and symmetric (150 mM KCl) conditions was ∼100 pS. DIDS caused a dramatic decrease in the channel activity (IC50 = 11.7 ± 3.1 μM) only when it was added to the cis side of a planar lipid membrane. The inhibition was accompanied by the significant prolongation of closings and the shortening
of openings within the burst as well as gaps between bursts were prolonged and durations of bursts were reduced. The blockade
was complete and irreversible when concentration of DIDS was increased up to 200 μM. Our data indicate that DIDS is an allosteric
blocker of mitochondrial anion channels and this specific effect could be used as a tool for reliable identification of anion
channels on the functional level. 相似文献
42.
Sheila K. Schueller 《Evolutionary ecology》2007,21(1):81-98
A match between floral and pollinator traits, such as that between unique island plants and pollinators, is often thought
to be the product of pollinator-mediated selection. I examined whether the floral morphology of an introduced hummingbird-pollinated
plant, Nicotiana glauca (tree tobacco, Solanaceae), is under selection by pollinators on the California Channel Islands where it is a recent colonist.
I first determined differences in floral morphology and pollinator composition between island and mainland populations of
N. glauca. I found that island plants have detectably longer corollas (on average 1 mm) and are visited by hummingbird species with
on average 1–2 mm longer bills than common mainland visitors. Corolla length differences were not found to be associated with
site abiotic differences. Flower size does not vary consistently with season and corolla width is very consistent across sites.
I tested whether island–mainland corolla length differences are the product of pollinator-mediated selection by measuring
phenotypic selection and per visit effectiveness. Contrary to expectations, a longer corolla was not consistently associated
with higher pollen transfer or seed count on the islands. Per visit effectiveness of longer and shorter-billed hummingbirds
did differ; however, effectiveness did not depend on corolla length. Although I failed to detect expected patterns of selection
for longer corollas on islands, I cannot rule out weak or past pollinator-mediated selection. It is also possible that despite
the apparent match between pollinator and floral traits, island–mainland differences in corolla length are instead due to
other environmental effects, selection unrelated to pollinators, or stochastic processes such as drift. 相似文献
43.
Over a decade ago, genetic studies identified a family of small integral membrane proteins, commonly referred to as copper transporters (CTRs) that are both required and sufficient for cellular copper uptake in a yeast genetic complementation assay. We recently used electron crystallography to determine a projection density map of the human high affinity transporter hCTR1 embedded into a lipid bilayer. At 6 Å resolution, this first glimpse of the structure revealed that hCTR1 is trimeric and possesses the type of radial symmetry that traditionally has been associated with the structure of certain ion channels such as potassium or gap junction channels. Representative for this particular type of architecture, a region of low protein density at the center of the trimer is consistent with the existence of a copper permeable pore along the center three-fold axis of the trimer. In this contribution, we will briefly discuss how recent structure–function studies correlate with the projection density map, and provide a perspective with respect to the cellular uptake of other transition metals. 相似文献
44.
The effect of seasonality on oxidative metabolism in Nacella (Patinigera) magellanica 总被引:1,自引:0,他引:1
Gabriela Malanga María Susana Estevez Jorge Calvo Doris Abele Susana Puntarulo 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2007,146(4):551
We studied the seasonal variation on aerobic metabolism and the response of oxidative stress parameters in the digestive glands of the subpolar limpet Nacella (P.) magellanica. Sampling was carried out from July (winter) 2002 to July 2003 in Beagle Channel, Tierra del Fuego, Argentina. Whole animal respiration rates increased in early spring as the animals spawned and remained elevated throughout summer and fall (winter: 0.09 ± 0.02 μmol O2 h− 1 g− 1; summer: 0.31 ± 0.06 μmol O2 h− 1 g− 1). Oxidative stress was assessed at the hydrophilic level as the ascorbyl radical content / ascorbate content ratio (A / AH−). The A / AH− ratio showed minimum values in winter (3.7 ± 0.2 10− 5 AU) and increased in summer (18 ± 5 10− 5 AU). A similar pattern was observed for lipid radical content (122 ± 29 pmol mg− 1 fresh mass [FW] in winter and 314 ± 45 pmol mg− 1 FW in summer), iron content (0.99 ± 0.07 and 2.7 ± 0.6 nmol mg− 1 FW in winter and summer, respectively) and catalase activity (2.9 ± 0.2 and 7 ± 1 U mg− 1 FW in winter and summer, respectively). Since nitrogen derived radicals are thought to be critically involved in oxidative metabolism in cells, nitric oxide content was measured and a significant difference in the content of the Fe–MGD–NO adduct in digestive glands from winter and summer animals was observed. Together, the data indicate that both oxygen and nitrogen radical generation rates in N. (P.) magellanica are strongly dependent on season. 相似文献
45.
Beno?te Bourdin Behzad Shakeri Marie-Philippe Tétreault Rémy Sauvé Sylvie Lesage Lucie Parent 《The Journal of biological chemistry》2015,290(5):2854-2869
L-type Ca2+ channels play a critical role in cardiac rhythmicity. These ion channels are oligomeric complexes formed by the pore-forming CaVα1 with the auxiliary CaVβ and CaVα2δ subunits. CaVα2δ increases the peak current density and improves the voltage-dependent activation gating of CaV1.2 channels without increasing the surface expression of the CaVα1 subunit. The functional impact of genetic variants of CACNA2D1 (the gene encoding for CaVα2δ), associated with shorter repolarization QT intervals (the time interval between the Q and the T waves on the cardiac electrocardiogram), was investigated after recombinant expression of the full complement of L-type CaV1.2 subunits in human embryonic kidney 293 cells. By performing side-by-side high resolution flow cytometry assays and whole-cell patch clamp recordings, we revealed that the surface density of the CaVα2δ wild-type protein correlates with the peak current density. Furthermore, the cell surface density of CaVα2δ mutants S755T, Q917H, and S956T was not significantly different from the cell surface density of the CaVα2δ wild-type protein expressed under the same conditions. In contrast, the cell surface expression of CaVα2δ D550Y, CaVα2δ S709N, and the double mutant D550Y/Q917H was reduced, respectively, by ≈30–33% for the single mutants and by 60% for the latter. The cell surface density of D550Y/Q917H was more significantly impaired than protein stability, suggesting that surface trafficking of CaVα2δ was disrupted by the double mutation. Co-expression with D550Y/Q917H significantly decreased CaV1.2 currents as compared with results obtained with CaVα2δ wild type. It is concluded that D550Y/Q917H reduced inward Ca2+ currents through a defect in the cell surface trafficking of CaVα2δ. Altogether, our results provide novel insight in the molecular mechanism underlying the modulation of CaV1.2 currents by CaVα2δ. 相似文献
46.
Jiraporn Ousingsawat Podchanart Wanitchakool Rainer Schreiber Manuela Wuelling Andrea Vortkamp Karl Kunzelmann 《The Journal of biological chemistry》2015,290(10):6270-6280
Anoctamin-6 (Ano6, TMEM16F) belongs to a family of putative Ca2+-activated Cl− channels and operates as membrane phospholipid scramblase. Deletion of Ano6 leads to reduced skeleton size, skeletal deformities, and mineralization defects in mice. However, it remains entirely unclear how a lack of Ano6 leads to a delay in bone mineralization by osteoblasts. The Na+/Ca2+ exchanger NCX1 was found to interact with Ano6 in a two-hybrid split-ubiquitin screen. Using human osteoblasts and osteoblasts from Ano6−/− and WT mice, we demonstrate that NCX1 requires Ano6 to efficiently translocate Ca2+ out of osteoblasts into the calcifying bone matrix. Ca2+-activated anion currents are missing in primary osteoblasts isolated from Ano6 null mice. Our findings demonstrate the importance of NCX1 for bone mineralization and explain why deletion of an ion channel leads to the observed mineralization defect: Ano6 Cl− currents are probably required to operate as a Cl− bypass channel, thereby compensating net Na+ charge movement by NCX1. 相似文献
47.
Prasanna K. Devaraneni Gregory M. Martin Erik M. Olson Qing Zhou Show-Ling Shyng 《The Journal of biological chemistry》2015,290(12):7980-7991
Small molecules that correct protein misfolding and misprocessing defects offer a potential therapy for numerous human diseases. However, mechanisms underlying pharmacological correction of such defects, especially in heteromeric complexes with structurally diverse constituent proteins, are not well understood. Here we investigate how two chemically distinct compounds, glibenclamide and carbamazepine, correct biogenesis defects in ATP-sensitive potassium (KATP) channels composed of sulfonylurea receptor 1 (SUR1) and Kir6.2. We present evidence that despite structural differences, carbamazepine and glibenclamide compete for binding to KATP channels, and both drugs share a binding pocket in SUR1 to exert their effects. Moreover, both compounds engage Kir6.2, in particular the distal N terminus of Kir6.2, which is involved in normal channel biogenesis, for their chaperoning effects on SUR1 mutants. Conversely, both drugs can correct channel biogenesis defects caused by Kir6.2 mutations in a SUR1-dependent manner. Using an unnatural, photocross-linkable amino acid, azidophenylalanine, genetically encoded in Kir6.2, we demonstrate in living cells that both drugs promote interactions between the distal N terminus of Kir6.2 and SUR1. These findings reveal a converging pharmacological chaperoning mechanism wherein glibenclamide and carbamazepine stabilize the heteromeric subunit interface critical for channel biogenesis to overcome defective biogenesis caused by mutations in individual subunits. 相似文献
48.
TRPV1 (transient receptor potential vanilloid 1) proteins are heat-activated nonselective cation channels. TRPV1 channels are polymodal in their function and exhibit multifaceted regulation with various molecular compounds. In this regard, phosphoinositides, particularly phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-phosphate, are important channel regulators. However, their effects on TRPV1 channel activity have not been conclusively determined. To characterize temperature-induced activation of TRPV1 in the presence of different phospholipids, we purified the TRPV1 protein from HEK-293 cells and incorporated it into planar lipid bilayers. In the presence of 2.5 μm phosphatidylinositol 4,5-bisphosphate, TRPV1 channels demonstrated rapid activation at 33–39 °C and achieved full channel opening at 42 °C. At this temperature range, TRPV1 heat activation exhibited steep temperature dependence (temperature coefficient (Q10) of 18), and the channel openings were accompanied by large changes in entropy and enthalpy, suggesting a substantial conformation change. At a similar temperature range, another phosphoinositide, phosphatidylinositol 4-phosphate, also potentiated heat activation of TRPV1, but with much lower efficiency. Negatively charged phosphatidylglycerol could also induce heat activation of TRPV1 channels, although with a small-conductance state. Our data demonstrate that phospholipids, specifically phosphoinositides, are important regulators of TRPV1 and are required for heat-induced channel activity. 相似文献
49.
Yuan Zhang Jiaoqian Ying Dongsheng Jiang Zhigang Chang Hua Li Guoqiang Zhang Shan Gong Xinghong Jiang Jin Tao 《The Journal of biological chemistry》2015,290(13):8644-8655
Recent studies have demonstrated that urotensin-II (U-II) plays important roles in cardiovascular actions including cardiac positive inotropic effects and increasing cardiac output. However, the mechanisms underlying these effects of U-II in cardiomyocytes still remain unknown. We show by electrophysiological studies that U-II dose-dependently potentiates L-type Ca2+ currents (ICa,L) in adult rat ventricular myocytes. This effect was U-II receptor (U-IIR)-dependent and was associated with a depolarizing shift in the voltage dependence of inactivation. Intracellular application of guanosine-5′-O-(2-thiodiphosphate) and pertussis toxin pretreatment both abolished the stimulatory effects of U-II. Dialysis of cells with the QEHA peptide, but not scrambled peptide SKEE, blocked the U-II-induced response. The phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin as well as the class I PI3K antagonist blocked the U-II-induced ICa,L response. Protein kinase C antagonists calphostin C and chelerythrine chloride as well as dialysis of cells with 1,2bis(2aminophenoxy)ethaneN,N,N′,N′-tetraacetic acid abolished the U-II-induced responses, whereas PKCα inhibition or PKA blockade had no effect. Exposure of ventricular myocytes to U-II markedly increased membrane PKCβ1 expression, whereas inhibition of PKCβ1 pharmacologically or by shRNA targeting abolished the U-II-induced ICa,L response. Functionally, we observed a significant increase in the amplitude of sarcomere shortening induced by U-II; blockade of U-IIR as well as PKCβ inhibition abolished this effect, whereas Bay K8644 mimicked the U-II response. Taken together, our results indicate that U-II potentiates ICa,L through the βγ subunits of Gi/o-protein and downstream activation of the class I PI3K-dependent PKCβ1 isoform. This occurred via the activation of U-IIR and contributes to the positive inotropic effect on cardiomyocytes. CH132799相似文献
50.
Wencheng Lin Zhiqiang Zhang Zhichao Xu Bin Wang Xiaoqi Li Hong Cao Yongqiang Wang Shijun J. Zheng 《The Journal of biological chemistry》2015,290(13):8500-8510
Infectious bursal disease (IBD) is an acute, highly contagious, and immunosuppressive avian disease caused by IBD virus (IBDV). Our previous report indicates that IBDV VP5 induces apoptosis via interaction with voltage-dependent anion channel 2 (VDAC2). However, the underlying molecular mechanism is still unclear. We report here that receptor of activated protein kinase C 1 (RACK1) interacts with both VDAC2 and VP5 and that they could form a complex. We found that overexpression of RACK1 inhibited IBDV-induced apoptosis in DF-1 cells and that knockdown of RACK1 by small interfering RNA induced apoptosis associated with activation of caspases 9 and 3 and suppressed IBDV growth. These results indicate that RACK1 plays an antiapoptotic role during IBDV infection via interaction with VDAC2 and VP5, suggesting that VP5 sequesters RACK1 and VDAC2 in the apoptosis-inducing process. 相似文献