beta-Arrestins are proteins that bind phosphorylated heterotrimeric GTP-binding protein (G protein)-coupled receptors (GPCRs) and contribute to the desensitization of GPCRs by uncoupling the signal transduction process. Resensitization of GPCR responsiveness involves agonist-mediated receptor sequestration. Overexpression of beta-arrestins in human embryonic kidney cells rescued the sequestration of beta 2-adrenergic receptor (beta 2AR) mutants defective in their ability to sequester, an effect enhanced by simultaneous overexpression of beta-adrenergic receptor kinase 1. Wild-type beta 2AR sequestration was inhibited by the overexpression of two beta-arrestin mutants. These findings suggest that beta-arrestins play an integral role in GPCR internalization and thus serve a dual role in the regulation of GPCR function.

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Background The coronavirus disease 2019 (COVID-19) pandemic has impacted many aspects of ST-segment elevation myocardial infarction (STEMI) care, including timely access to primary percutaneous coronary intervention (PPCI). Objectives The goal of the NACMI (North American COVID-19 and STEMI) registry is to describe demographic characteristics, management strategies, and outcomes of COVID-19 patients with STEMI. Methods A prospective, ongoing observational registry was created under the guidance of 3 cardiology societies. STEMI patients with confirmed COVID+ (group 1) or suspected (person under investigation [PUI]) (group 2) COVID-19 infection were included. A group of age- and sex-matched STEMI patients (matched to COVID+ patients in a 2:1 ratio) treated in the pre-COVID era (2015 to 2019) serves as the control group for comparison of treatment strategies and outcomes (group 3). The primary outcome was a composite of in-hospital death, stroke, recurrent myocardial infarction, or repeat unplanned revascularization. Results As of December 6, 2020, 1,185 patients were included in the NACMI registry (230 COVID+ patients, 495 PUIs, and 460 control patients). COVID+ patients were more likely to have minority ethnicity (Hispanic 23%, Black 24%) and had a higher prevalence of diabetes mellitus (46%) (all p < 0.001 relative to PUIs). COVID+ patients were more likely to present with cardiogenic shock (18%) but were less likely to receive invasive angiography (78%) (all p < 0.001 relative to control patients). Among COVID+ patients who received angiography, 71% received PPCI and 20% received medical therapy (both p < 0.001 relative to control patients). The primary outcome occurred in 36% of COVID+ patients, 13% of PUIs, and 5% of control patients (p < 0.001 relative to control patients). Conclusions COVID+ patients with STEMI represent a high-risk group of patients with unique demographic and clinical characteristics. PPCI is feasible and remains the predominant reperfusion strategy, supporting current recommendations.

The TRITON-TIMI 38 platelet substudy shows that prasugrel results in greater inhibition of ADP-mediated platelet function in ACS patients than clopidogrel, supporting the hypothesis that greater platelet inhibition leads to a lower incidence of ischaemic events and more bleeding both early and late following PCI.

Treatment with percutaneous myocardial laser revascularization provides no benefit beyond that of a similar sham procedure in patients blinded to their treatment status.

Delays in door-to-balloon time impact late survival in high-risk but not low-risk patients and in patients presenting early but not late after the onset of symptoms. These findings have implications for the triage of patients for primary PCI.

A clone for the iron-responsive element (IRE)-binding protein (IRE-BP) has been transfected and expressed in mouse fibroblasts. The IRE-BP gene product binds IREs with high affinity and specificity. Amino acid alignments reveal that the IRE-BP is 30% identical to mitochondrial aconitase. The 18 active site residues of mitochondrial aconitase are identical to those in the IRE-BP, suggesting that the IRE-BP may possess aconitase activity. After purification of native IRE-BP and immunoaffinity purification of transfected and expressed IRE-BP, we demonstrate that the purified IRE-BP has aconitase activity.

Several cDNA clones coding for the high molecular weight (a) subunit of the voltage-sensitive Na channel have been selected by immunoscreening a rat brain cDNA library constructed in the expression vector Xgtll. As will be reported elsewhere, the amino acid sequence translated from the DNA sequence shows considerable homology to that reported for the Electrophorus eketricus electroplax Na channel. Several of the cDNA inserts hybridized with a low-abundance 9-kilobase RNA species from rat brain, muscle, and heart. Sucrose-gradient fractionation of rat brain poly(A) RNA yielded a high molecular weight fraction containing this mRNA, which resulted in functional Na channels when injected into oocytes. This fraction contained undetectable amounts of low molecular weight RNA. The high molecular weight Na channel RNA was selected from rat brain poly(A) RNA by hybridization to a single-strand antisense cDNA clone. Translation of this RNA in Xenopus oocytes resulted in the appearance of tetrodotoxin-sensitive voltage-sensitive Na channels in the oocyte membrane. These results demonstrate that mRNA encoding the a subunit of the rat brain Na channel, in the absence of any ,B-subunit mRNA, is sufficient for translation to give functional channels in oocytes.The initial depolarization event in the propagation of an action potential in nerve and muscle is due to the opening of voltage-sensitive Na channels. This channel-protein complex has been purified from Electrophorus electricus electroplax membranes (1), rat muscle (2), chicken cardiac muscle (3), and rat brain (4). As isolated, the electroplax protein consists of a single large subunit of Mr 260,000 (5-7) encompassing 1820 amino acids (8). Similarly, the chicken heart protein comprises one subunit of Mr 230,000-270,000 (3). However, as isolated, the rat brain Na-channel complex contains one large subunit (a) with a Mr of =260,000 as determined by NaDodSO4/PAGE, and two associated small subunits, (B1 and ,82, ofMr 36,000 and 33,000, respectively (9, 10). The rat skeletal muscle channel also contains both a and at least one /3 subunit (11,12). In adult rat brain, the a and ,82 subunits are covalently attached by disulfide bonds (9). Both the rat and eel protein complexes have been reconstituted into phospholipid vesicles, with restoration of toxin-induced activation of Na permeability (13-16).The cDNA coding for the electroplax protein has been molecularly cloned and its sequence has been determined (8). Furthermore, while the present manuscript was in the proof stage, the cloning and sequencing of cDNAs coding for rat brain Na channels was reported (17). This latter study shows that there are at least two related a-subunit Na-channel mRNAs in rat brain, denoted I and II, and there is possibly a third.The functional significance of the small subunits in rat brain is not known. Schmidt et al. (18) present data suggesting that disulfide linkage of the a and ,2 subunits, insertion into the cell-surface membrane, and attainment of a functional conformation are closely...