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Andrei V. Stepanov

Other affiliations: Ohio State University
Bio: Andrei V. Stepanov is an academic researcher from Russian Academy of Sciences. The author has contributed to research in topics: Strobilurins & Stereoselectivity. The author has an hindex of 7, co-authored 27 publications receiving 124 citations. Previous affiliations of Andrei V. Stepanov include Ohio State University.

Papers
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Journal ArticleDOI
TL;DR: It is concluded that in a process whereby leak begets leak, augmented RyR2 activity modulates mitochondrial Ca 2+ handling, promoting mito-ROS emission and driving further channel activity in a proarrhythmic feedback cycle in the diseased heart.
Abstract: Cardiac disease is associated with deleterious emission of mitochondrial reactive oxygen species (mito-ROS), as well as enhanced oxidation and activity of the sarcoplasmic reticulum (SR) Ca2+ release channel, the ryanodine receptor (RyR2). The transfer of Ca2+ from the SR via RyR2 to mitochondria is thought to play a key role in matching increased metabolic demand during stress. In this study, we investigated whether augmented RyR2 activity results in self-imposed exacerbation of SR Ca2+ leak, via altered SR-mitochondrial Ca2+ transfer and elevated mito-ROS emission. Fluorescent indicators and spatially restricted genetic ROS probes revealed that both pharmacologically and genetically enhanced RyR2 activity, in ventricular myocytes from rats and catecholaminergic polymorphic ventricular tachycardia (CPVT) mice, respectively, resulted in increased ROS emission under β-adrenergic stimulation. Expression of mitochondrial Ca2+ probe mtRCamp1h revealed diminished net mitochondrial [Ca2+] with enhanced SR Ca2+ leak, accompanied by depolarization of the mitochondrial matrix. While this may serve as a protective mechanism to prevent mitochondrial Ca2+ overload, protection is not complete and enhanced mito-ROS emission resulted in oxidation of RyR2, further amplifying proarrhythmic SR Ca2+ release. Importantly, the effects of augmented RyR2 activity could be attenuated by mitochondrial ROS scavenging, and experiments with dominant-negative paralogs of the mitochondrial Ca2+ uniporter (MCU) supported the hypothesis that SR-mitochondria Ca2+ transfer is essential for the increase in mito-ROS. We conclude that in a process whereby leak begets leak, augmented RyR2 activity modulates mitochondrial Ca2+ handling, promoting mito-ROS emission and driving further channel activity in a proarrhythmic feedback cycle in the diseased heart.

61 citations

Journal ArticleDOI
TL;DR: In this paper, reactions of alkenes with nitrogen oxides and other nitrosating and nitrating reagents are considered. And the bibliography includes 134 references including 134 references.
Abstract: Reactions of alkenes with nitrogen oxides and other nitrosating and nitrating reagents are considered. The bibliography includes 134 references.

30 citations

Journal ArticleDOI
TL;DR: The first demonstration of local, transient Ca2+entry (LoCE) events, which comprise cardiac SOCE, are provided and it is reported that both LoCEs and their underlying protein machinery are concentrated at the intercalated disk (ID).
Abstract: Store-operated Ca2+ entry (SOCE), a major Ca2+ signaling mechanism in non-myocyte cells, has recently emerged as a component of Ca2+ signaling in cardiac myocytes Though it has been reported to play a role in cardiac arrhythmias and to be upregulated in cardiac disease, little is known about the fundamental properties of cardiac SOCE, its structural underpinnings or effector targets An even greater question is how SOCE interacts with canonical excitation-contraction coupling (ECC) We undertook a multiscale structural and functional investigation of SOCE in cardiac myocytes from healthy mice (wild type; WT) and from a genetic murine model of arrhythmic disease (catecholaminergic ventricular tachycardia; CPVT) Here we provide the first demonstration of local, transient Ca2+ entry (LoCE) events, which comprise cardiac SOCE Although infrequent in WT myocytes, LoCEs occurred with greater frequency and amplitude in CPVT myocytes CPVT myocytes also evidenced characteristic arrhythmogenic spontaneous Ca2+ waves under cholinergic stress, which were effectively prevented by SOCE inhibition In a surprising finding, we report that both LoCEs and their underlying protein machinery are concentrated at the intercalated disk (ID) Therefore, localization of cardiac SOCE in the ID compartment has important implications for SOCE-mediated signaling, arrhythmogenesis and intercellular mechanical and electrical coupling in health and disease

29 citations

Journal ArticleDOI
TL;DR: In this paper, a method for the stereoselective synthesis of substituted 4aS*,7aS*-hexahydrocyclopenta[c]pyran-3(1H)-one, promising synthon of isoprostanes, has been developed based on the intramolecular dipolar [3+2] cycloaddition of silyl nitronates generated from 6-nitrohex-1-ene derivative.
Abstract: A method for the stereoselective synthesis of substituted 4aS*,7aS*-hexahydrocyclopenta[c]pyran-3(1H)-one, promising synthon of isoprostanes, has been developed based on the intramolecular dipolar [3+2] cycloaddition of silyl nitronates generated from 6-nitrohex-1-ene derivative.

10 citations

Journal ArticleDOI
TL;DR: Heterogeneous catalyst ZIF-8, a representative of zeolitic imidazolate framework family, promotes the Henry reaction between aldehydes and nitromethane as discussed by the authors.

10 citations


Cited by
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Journal ArticleDOI
TL;DR: The development by Ohmori and co-workers of a fluorinative variant of the Mitsunobu reaction, involving the electrooxidative generation and subsequent thermal decomposition of alkoxytriphenylphosphonium tetrafluoroborates, allowing for the conversion of alcohols to the corresponding alkyl fluorides with inversion of configuration.
Abstract: The Balz-Schiemann synthesis of aryl fluorides via the thermal decomposition of aryl diazonium tetrafluoroborate salts represents both the earliest and the most proverbial example of the BF4 ion as a nucleophilic fluoride source. Mechanistic studies of the Balz-Schiemann reaction have accrued strong experimental support for an SN1 mechanism via the intermediacy of an aryl cation, which is quenched by fluoride transfer directly from the BF4 ion. A notable advance in this area has been the development by Ohmori and co-workers of a fluorinative variant of the Mitsunobu reaction, involving the electrooxidative generation and subsequent thermal decomposition of alkoxytriphenylphosphonium tetrafluoroborates, allowing for the conversion of alcohols to the corresponding alkyl fluorides with inversion of configuration. Although stereoselectivity during C-F bond formation for reactions proceeding via (putative) carbocation intermediates can be highly variable, the ring-opening of strained rings or ?iranium intermediates via fluoride transfer from fluoroborate ions typically proceeds with high stereoselectivity.

141 citations

Journal ArticleDOI
TL;DR: The purpose of this review is to provide an overview of all methods of direct alkene diamination, metal-mediated or otherwise.

123 citations

Journal ArticleDOI
TL;DR: In this article, the authors provided updated insights into the key role of mitochondrial quality control (MQC) mechanisms in coronary ECs and microvascular dysfunction in MI, and discussed the option of MQC as a novel therapeutic target to delay, reverse or repair coronary micro-vascular damage in MI.
Abstract: Endothelial cells (ECs) constitute the innermost layer in all blood vessels to maintain the structural integrity and microcirculation function for coronary microvasculature. Impaired endothelial function is demonstrated in various cardiovascular diseases including myocardial infarction (MI), which is featured by reduced myocardial blood flow as a result of epicardial coronary obstruction, thrombogenesis, and inflammation. In this context, understanding the cellular and molecular mechanisms governing the function of coronary ECs is essential for the early diagnosis and optimal treatment of MI. Although ECs contain relatively fewer mitochondria compared with cardiomyocytes, they function as key sensors of environmental and cellular stress, in the regulation of EC viability, structural integrity and function. Mitochondrial quality control (MQC) machineries respond to a broad array of stress stimuli to regulate fission, fusion, mitophagy and biogenesis in mitochondria. Impaired MQC is a cardinal feature of EC injury and dysfunction. Hence, medications modulating MQC mechanisms are considered as promising novel therapeutic options in MI. Here in this review, we provide updated insights into the key role of MQC mechanisms in coronary ECs and microvascular dysfunction in MI. We also discussed the option of MQC as a novel therapeutic target to delay, reverse or repair coronary microvascular damage in MI. Contemporary available MQC-targeted therapies with potential clinical benefits to alleviate coronary microvascular injury during MI are also summarized.

104 citations

Journal ArticleDOI
TL;DR: In this paper, a method for the oxidative nitration of alkenes using a combination of tert-butyl nitrite and molecular oxygen to give β-nitro alcohols and their nitrate derivatives has been developed.
Abstract: A method for the oxidative nitration of alkenes using a combination of tert-butyl nitrite and molecular oxygen to give β-nitro alcohols and their nitrate derivatives has been developed. The present reaction provides a practical method for the synthesis of nitro compounds because of the mild reaction conditions, the use of inexpensive reagents and a simple experimental procedure.

91 citations