Allitridin Reduces <b><i>I</i></b>_Kr Current by Disrupting the Trafficking of Human Ether-à-Go-Go-Related Gene Channels

Abstract

Objectives: To investigate the effects of allitridin on human ether-à-go-go-related gene (hERG) channels. Methods: We used whole-cell patch clamping and laser confocal scanning microscopy to evaluate the effects of allitridin on hERG currents and the membrane expression of the hERG protein expressed in HEK 293 cells. Results: The amplitude of I_Kr showed a concentration-dependent decrease with increasing allitridin concentration. Additionally, alterations in the gating properties of hERG channels were also confirmed. Allitridin does not alter the voltage- and time-dependent activation of hERG channels, the gating properties of hERG channel inactivation over time or the recovery from inactivation, but allitridin does cause alterations in the steady-state inactivation and the deactivation of hERG channels. We further evaluated the influence of allitridin on membrane expression of the hERG protein. Images of allitridin-treated cells showed a reduction in hERG protein on the membrane and retention in the cytoplasm. Conclusions: To the best of our knowledge this is the first study to show that allitridin reduces the I_Kr current by impairing the trafficking of hERG channels. The results may demonstrate that allitridin could be a promising candidate for the prevention and treatment of arrhythmia-related diseases.

Cysteine-Reactive Free ISG15 Generates IL-1β–Producing CD8α+ Dendritic Cells at the Site of Infection

“…Similar to ubiquitin, ISG15 can be conjugated to intracellular proteins through E1 (UBE1L), E2 (UbcH8), and E3 conjugating enzymes. ISGylation can modify protein function (1) and extensive studies have elucidated its role, mostly in the context of viral infections (1–4). Recently the function of intracellular conjugated ISG15 has been extended to bacterial infections where it was found that Listeria infection induces ISGylation in non-phagocytic cells (5).…”

Allicin disrupts cardiac Cav1.2 channels via trafficking

“…Allicin was prepared as previously described (Li G et al. 2014). Allicin (74265, Sigma-Aldrich, Merck KGaA, Darmstadt, Germany) was dissolved in dimethyl sulphoxide (DMSO) at a concentration of 10 mg/mL and stored at −4 °C.…”

“…The choice of the experimental concentrations was based on the results of the cell viability experiment and the results of the previous studies of allicin of our team (Li G et al. 2014). Lysates were centrifuged at 10,000 g for 5 min, and protein content was analyzed with BCA Protein Assay Kit (HyClone-Pierce 23225).…”

“…Images of cells were obtained using an FV1000 laser scanning microscope (Leica DM2500, Germany) (Li G et al. 2014).…”

Acute Pancreatitis Masquerading as Inferior Wall Myocardial Infarction: A Review

“…Although ischemic ECG findings have been known to present in pancreatitis from the 1930s, these generally lacked 12-lead ECG data and standardized nomenclature [3, 4]. Since Bauerlein and Stobbe in 1954 [5], 36 instances of such mimicry have been noted, as shown in Table 1,Table 2, and Table 3 [5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38] (clinical course, diagnostic testing, and patient outcome was not specified in one report and was omitted in the prevalence values for the respective categories). An inferior wall infarction pattern appears to be the most frequent (44.4%, or 16/36 cases).…”