Reductions in the blood supply produce considerable injury if the duration of ischemia is prolonged. Paradoxically, restoration of perfusion to ischemic organs can exacerbate tissue damage and extend the size of an evolving infarct. Being highly metabolic organs, the heart and brain are particularly vulnerable to the deleterious effects of ischemia/reperfusion (I/R). While the pathogenetic mechanisms contributing to I/R-induced tissue injury and infarction are multifactorial, the relative importance of each contributing factor remains unclear. However, an emerging body of evidence indicates that the generation of reactive oxygen species (ROS) by mitochondria plays a critical role in damaging cellular components and initiating cell death. In this review, we summarize our current understanding of the mechanisms whereby mitochondrial ROS generation occurs in I/R and contributes to myocardial infarction and stroke. In addition, mitochondrial ROS have been shown to participate in preconditioning by several pharmacologic agents that target potassium channels (e.g., ATP-sensitive potassium (mKATP) channels or large conductance, calcium-activated potassium (mBKCa) channels) to activate cell survival programs that render tissues and organs more resistant to the deleterious effects of I/R. Finally, we review novel therapeutic approaches that selectively target mROS production to reduce postischemic tissue injury, which may prove efficacious in limiting myocardial dysfunction and infarction and abrogating neurocognitive deficits and neuronal cell death in stroke.
Resveratrol is a natural polyphenol found in grapes and wine and has been associated with protective effects against cardiovascular diseases. In vitro, both resveratrol preconditioning (RPC) and ischemic preconditioning (IPC) require activation of sirtuin 1 (SIRT1), an NAD+-dependent deacetylases, to induce neuroprotection against cerebral ischemia. In the present study, we tested two hypotheses: a) that neuroprotection against cerebral ischemia can be induced by RPC in vivo; and b) that RPC neuroprotection involves alterations in mitochondrial function via the SIRT1 target mitochondrial uncoupling protein 2 (UCP2). IPC was induced by two minutes of global ischemia (temporary bilateral carotid artery occlusion with hypotension), and RPC, by intraperitoneal injection of resveratrol at 10, 50 and 100 mg/Kg dosages. 48 hours later, we compared the neuroprotective efficacy of RPC and IPC in vulnerable CA1 hippocampal pyramidal neurons using a rat model of asphyxial cardiac arrest (ACA). SIRT1 activity was measured using a SIRT1-specific fluorescent enzyme activity assay. In hippocampal mitochondria isolated 48 hours after IPC or RPC, we measured UCP2 levels, membrane potential, respiration, and the mitochondrial ATP synthesis efficiency (ADP/O ratio). Both IPC and RPC induced tolerance against brain injury induced by cardiac arrest in this in vivo model. IPC increased SIRT1 activity at 48 hours, while RPC increased SIRT1 activity at 1 hour but not 48 hours after treatment in hippocampus. Resveratrol significantly decreased UCP2 levels by 35% compared to sham-treated rats. The SIRT1-specific inhibitor sirtinol abolished the neuroprotection afforded by RPC and the decrease in UCP2 levels. Finally, RPC significantly increased the ADP/O ratio in hippocampal mitochondria reflecting enhanced ATP synthesis effieciency. In conclusion, in vivo resveratrol pretreatment confers neuroprotection similar to IPC via the SIRT1-UCP2 pathway.
The potential of association mapping (AM) and genomic selection (GS) has not yet been explored for investigating resistance to soybean cyst nematode (SCN), the most destructive pest affecting soybean. We genotyped 282 representative accessions from the University of Minnesota soybean breeding program using a genome-wide panel of 1536 single nucleotide polymorphism (SNP) markers and evaluated plant responses to SCN HG type 0. After adjusting for population structure, AM detected significant signals at two loci corresponding to rhg1 and FGAM1 plus a third locus located at the opposite end of chromosome 18. Our analysis also identified a discontinuous long-range haplotype of over 600 kb around rhg1 locus associated with resistance to SCN HG type 0. The same phenotypic and genotypic datasets were then used to access GS accuracy for prediction of SCN resistance in the presence of major genes through a sixfold cross-validation study. Genomic selection using the full marker set produced average prediction accuracy ranging from 0.59 to 0.67 for SCN resistance, significantly more accurate than marker-assisted selection (MAS) strategies using two rhg1-associated DNA makers. Reducing the number of markers to 288 SNPs in the GS training population had little effect on genomic prediction accuracy. This study demonstrates that AM can be an effective genomic tool for identifying genes of interest in diverse germplasm. The results also indicate that improved MAS and GS can enhance breeding efficiency for SCN resistance in existing soybean improvement programs.
Sudden death syndrome (SDS), caused by Fusarium virguliforme, has spread to northern soybean growing regions in the US causing significant yield losses. The objectives of this study were to identify loci underlying variation in plant responses to SDS through association mapping (AM) and to assess prediction accuracy of genomic selection (GS) in a panel of early maturing soybean germplasm. A set of 282 soybean breeding lines was selected from the University of Minnesota soybean breeding program and then genotyped using a genome-wide panel of 1536 single-nucleotide polymorphism markers. Four resistance traits, root lesion severity (RLS), foliar symptom severity (FSS), root retention (RR), and dry matter reduction (DMR), were evaluated using soil inoculation in the greenhouse. AM identified significant peaks in genomic regions of known SDS resistance quantitative trait loci cqSDS001, cqRfs4, and SDS11-2. Additionally, two novel loci, one on chromosome 3 and another on chromosome 18, were tentatively identified. A ninefold cross-validation scheme was used to assess the prediction accuracy of GS for SDS resistance. The prediction accuracy of single-trait GS (ST-GS) was 0.64 for RLS, but less than 0.30 for RR, DMR, and FSS. Compared to ST-GS, none of multi-trait GS (MT-GS) models significantly improved the prediction accuracy due to weak correlations between the four traits. This study suggests both AM and GS hold promise for implementation in genetic improvement of SDS resistance in existing soybean breeding programs.Electronic supplementary materialThe online version of this article (doi:10.1007/s11032-015-0324-3) contains supplementary material, which is available to authorized users.
Using next-generation DNA sequencing, it was possible to clarify the genetic relationships of Avena species and deduce the likely pathway from which hexaploid oat was formed by sequential polyploidization events. A sequence-based diversity study was conducted on a representative sample of accessions from species in the genus Avena using genotyping-by-sequencing technology. The results show that all Avena taxa can be assigned to one of four major genetic clusters: Cluster 1 = all hexaploids including cultivated oat, Cluster 2 = AC genome tetraploids, Cluster 3 = C genome diploids, Cluster 4 = A genome diploid and tetraploids. No evidence was found for the existence of discrete B or D genomes. Through a series of experiments involving the creation of in silico polyploids, it was possible to deduce that hexaploid oat likely formed by the fusion of an ancestral diploid species from Cluster 3 (A. clauda, A. eriantha) with an ancestral diploid species from Cluster 4D (A. longiglumis, A. canariensis, A. wiestii) to create the ancestral tetraploid from Cluster 2 (A. magna, A. murphyi, A. insularis). Subsequently, that ancestral tetraploid fused again with another ancestral diploid from Cluster 4D to create hexaploid oat. Based on the geographic distribution of these species, it is hypothesized that both the tetraploidization and hexaploidization events may have occurred in the region of northwest Africa, followed by radiation of hexaploid oat to its current worldwide distribution. The results from this study shed light not only on the origins of this important grain crop, but also have implications for germplasm collection and utilization in oat breeding.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.