Low signaling efficiency from receptor to effector in olfactory transduction: A quantified ligand-triggered GPCR pathway.

G protein-coupled receptor (GPCR) signaling is ubiquitous. As an archetype of this signaling motif, rod phototransduction has provided many fundamental, quantitative details, including a dogma that one active GPCR molecule activates a substantial number of downstream G protein/enzyme effector complexes. However, rod phototransduction is light-activated, whereas GPCR pathways are predominantly ligand-activated.

Transcriptional regulation of intermolecular Ca signaling in hibernating ground squirrel cardiomyocytes: The myocardin-junctophilin axis.

The contraction of heart cells is controlled by the intermolecular signaling between L-type Ca channels (LCCs) and ryanodine receptors (RyRs), and the nanodistance between them depends on the interaction between junctophilin-2 (JPH2) in the sarcoplasmic reticulum (SR) and caveolin-3 (CAV3) in the transversal tubule (TT). In heart failure, decreased expression of JPH2 compromises LCC-RyR communication leading to deficient blood-pumping power. In the present study, we found that JPH2 and CAV3 transcription was concurrently regulated by serum response factor (SRF) and myocardin.

Calcium-activated chloride channels clamp odor-evoked spike activity in olfactory receptor neurons.

The calcium-activated chloride channel anoctamin-2 (Ano2) is thought to amplify transduction currents in olfactory receptor neurons (ORNs), a hypothesis supported by previous studies in dissociated neurons from Ano2 mice. Paradoxically, despite a reduction in transduction currents in Ano2 ORNs, their spike output for odor stimuli may be higher. We examined the role of Ano2 in ORNs in their native environment in freely breathing mice by imaging activity in ORN axons as they arrive in the olfactory bulb glomeruli.

Ca-activated Cl current predominates in threshold response of mouse olfactory receptor neurons.

In mammalian olfactory transduction, odorants activate a cAMP-mediated signaling pathway that leads to the opening of cyclic nucleotide-gated (CNG), nonselective cation channels and depolarization. The Ca influx through open CNG channels triggers an inward current through Ca-activated Cl channels (ANO2), which is expected to produce signal amplification. However, a study on an mouse line reported no elevation in the behavioral threshold of odorant detection compared with wild type (WT).

Cyclic-nucleotide-gated cation current and Ca2+-activated Cl current elicited by odorant in vertebrate olfactory receptor neurons.

Olfactory transduction in vertebrate olfactory receptor neurons (ORNs) involves primarily a cAMP-signaling cascade that leads to the opening of cyclic-nucleotide-gated (CNG), nonselective cation channels. The consequent Ca influx triggers adaptation but also signal amplification, the latter by opening a Ca-activated Cl channel (ANO2) to elicit, unusually, an inward Cl current. Hence the olfactory response has inward CNG and Cl components that are in rapid succession and not easily separable.

Ultrastructural uncoupling between T-tubules and sarcoplasmic reticulum in human heart failure.

Aims: Chronic heart failure is a complex clinical syndrome with impaired myocardial contractility. In failing cardiomyocytes, decreased signalling efficiency between the L-type Ca(2+) channels (LCCs) in the plasma membrane (including transverse tubules, TTs) and the ryanodine receptors (RyRs) in the sarcoplasmic reticulum (SR) underlies the defective excitation-contraction (E-C) coupling. It is therefore intriguing to know how the LCC-RyR signalling apparatus is remodelled in human heart failure.

In vivo suppression of microRNA-24 prevents the transition toward decompensated hypertrophy in aortic-constricted mice.

Rationale: During the transition from compensated hypertrophy to heart failure, the signaling between L-type Ca(2+) channels in the cell membrane/T-tubules and ryanodine receptors in the sarcoplasmic reticulum becomes defective, partially because of the decreased expression of a T-tubule-sarcoplasmic reticulum anchoring protein, junctophilin-2. MicroRNA (miR)-24, a junctophilin-2 suppressing miR, is upregulated in hypertrophied and failing cardiomyocytes.

Objective: To test whether miR-24 suppression can protect the structural and functional integrity of L-type Ca(2+) channel-ryanodine receptor signaling in hypertrophied cardiomyocytes.

Mir-24 regulates junctophilin-2 expression in cardiomyocytes.

Rationale: Failing cardiomyocytes exhibit decreased efficiency of excitation-contraction (E-C) coupling. The downregulation of junctophilin-2 (JP2), a protein anchoring the sarcoplasmic reticulum to T-tubules, has been identified as a major mechanism underlying the defective E-C coupling. However, the regulatory mechanism of JP2 remains unknown.

Ultrastructural remodelling of Ca(2+) signalling apparatus in failing heart cells.

Aims: The contraction of a heart cell is controlled by Ca(2+)-induced Ca(2+) release between L-type Ca(2+) channels (LCCs) in the cell membrane/T-tubules (TTs) and ryanodine receptors (RyRs) in the junctional sarcoplasmic reticulum (SR). During heart failure, LCC-RyR signalling becomes defective. The purpose of the present study was to reveal the ultrastructural mechanism underlying the defective LCC-RyR signalling and contractility.

The mechanism of kinetic inhibition of Cu(II)-induced oxidation of low density lipoprotein by lanthanide ions.

Oral administration of lanthanum chloride (LaCl(3)) was reported to inhibit atherosclerosis in experimental animals, but the mechanism was not clear. In the present work, the effects of La(III) and other lanthanide ions (Ln(III)) on Cu(II)-induced oxidation of isolated low-density lipoprotein (LDL) and the related mechanism were investigated. By monitoring the formation of conjugated dienes (CD), low concentrations of La(III), Gd(III) and Y(III) were found to inhibit Cu(II)-induced LDL oxidation kinetically, as characterized by the prolongation of the lag time, the decrease of the maximal accumulation of CD, and the maximal rate of CD accumulation.

Apotransferrin is internalized and distributed in the same way as holotransferrin in K562 cells.

Transferrin (Tf), a naturally existing protein, has received considerable attention in the area of drug targeting since it is biodegradable, non-toxic, and non-immunogenic. The efficient cellular uptake of Tf shows it has potential in the delivery of anti-cancer drugs, proteins, and therapeutic genes into proliferating malignant cells that overexpress transferrin receptor (TfR). In human serum, about 30% of Tf exists in the iron-saturated form (Fe(2)-Tf) and the remainder exists as apotransferrin (apo-Tf).

[La accumulation and microstructure change of leg bones of rats fed with La(NO(3))(3) in low dosage for a long term].

Objective: To study La accumulation and microstructure change of leg bones of rats fed with La(NO(3))(3) in low dosage for a long term.

Methods: After the rats were fed by La(NO(3))(3) in dosage of 2 mg x (kg(-1) x d(-1)) for 6 months, the contents of La and Ca,P in the leg bones were determined by ICP MS and spectrophotometry; the microstructure changes of the leg bones were investigated by electron microscopy and X-ray powder diffraction.

Results: In the leg bones of tested rats, the contents of La and P increased greatly, and those of Ca did not change obviously, so that Ca/P ratio values decreased in comparison with the control group.

[Effects of lanthanum on alkaline phosphatase].

Objective: To investigate the effects of lanthanum on the activities of two kinds of alkaline phosphatase (AP)-rat liver AP and bovine intestine AP, and the preliminary mechanism involved.

Methods: A traditional colorimetric method was used to measure the activity of AP. The influence of La3+ on the intrinsic fluorescence of protein was studied by the method of fluorescence titration into the AP solution by LaCl3.

Complexation of ytterbium to human transferrin and its uptake by K562 cells.

There is an increasing interest in the use of lanthanides in medicine. However, the mechanism of their accumulation in cells is not well understood. Lanthanide cations are similar to ferric ions with regard to transferrin binding, suggesting transferrin-receptor mediated transport is possible; however, this has not yet been confirmed.