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Cardiac tissue undergoes changes during ischemia-reperfusion (I-R) that compromise its normal function. Cell death is one of the consequences of such damage, as well as diminution in nitric oxide (NO) content. This signaling molecule regulates the function of the cardiovascular system through dependent and independent effects of cyclic guanosine monophosphate (cGMP). The independent cGMP pathway involves post-translational modification of proteins by S-nitrosylation. Studies in vitro have shown that NO inhibits the activity of caspases and calpains through S-nitrosylation of a cysteine located in their catalytic site, so we propose to elucidate if the regulatory mechanisms of NO are related with changes in S-nitrosylation of cell death proteins in the ischemic-reperfused myocardium. We used two compounds that increase the levels of NO by different mechanisms: Prolame, an amino-estrogenic compound with antiplatelet and anticoagulant effects that induces the increase of NO levels in vivo by activating the endothelial nitric oxide synthase (eNOS) and that has not been tested as a potential inhibitor of apoptosis. On the other hand, S-Nitroso-N-acetylpenicillamine (SNAP), a synthetic NO donor that has been shown to decrease cell death after inducing hypoxia-reoxygenation in cell cultures. Main experimental groups were Control, I-R, I-R+Prolame and I-R+SNAP. Additional groups were used to evaluate the NO action pathways. Contractile function represented as heart rate and ventricular pressure was evaluated in a Langendorff system. Infarct size was measured with 2,3,5-triphenyltetrazolium chloride stain. NO content was determined indirectly by measuring nitrite levels with the Griess reaction and cGMP content was measured by Enzyme-Linked ImmunoSorbent Assay. DNA integrity was evaluated by DNA laddering visualized on an agarose gel and by Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling assay. Activities of caspase-3, caspase-8, caspase-9 and calpain-1 were evaluated spectrophotometrically and the content of caspase-3 and calpain-1 by western blot. S-nitrosylation of caspase-3 and calpain-1 was evaluated by labeling S-nitrosylated cysteines. Our results show that both Prolame and SNAP increased NO content and improved functional recovery in post-ischemic hearts. cGMP-dependent and S-nitrosylation pathways were activated in both groups, but the cGMP-independent pathway was preferentially activated by SNAP, which induced higher levels of NO than Prolame. Although SNAP effectively diminished the activity of all the proteases, a correlative link between the activity of these proteases and S-nitrosylation was not fully established.
Pubmed ID: 31392096
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View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE, documented May 10, 2017. A pilot effort that has developed a centralized, web-based biospecimen locator that presents biospecimens collected and stored at participating Arizona hospitals and biospecimen banks, which are available for acquisition and use by researchers. Researchers may use this site to browse, search and request biospecimens to use in qualified studies. The development of the ABL was guided by the Arizona Biospecimen Consortium (ABC), a consortium of hospitals and medical centers in the Phoenix area, and is now being piloted by this Consortium under the direction of ABRC. You may browse by type (cells, fluid, molecular, tissue) or disease. Common data elements decided by the ABC Standards Committee, based on data elements on the National Cancer Institute''s (NCI''s) Common Biorepository Model (CBM), are displayed. These describe the minimum set of data elements that the NCI determined were most important for a researcher to see about a biospecimen. The ABL currently does not display information on whether or not clinical data is available to accompany the biospecimens. However, a requester has the ability to solicit clinical data in the request. Once a request is approved, the biospecimen provider will contact the requester to discuss the request (and the requester''s questions) before finalizing the invoice and shipment. The ABL is available to the public to browse. In order to request biospecimens from the ABL, the researcher will be required to submit the requested required information. Upon submission of the information, shipment of the requested biospecimen(s) will be dependent on the scientific and institutional review approval. Account required. Registration is open to everyone., documented September 29, 2016. A workbench tool to make existing population genetic software more accessible and to facilitate the integration of new tools for analyzing patterns of DNA sequence variation, within a phylogenetic context. Collectively, SNAP tools can serve as a bridge between theoretical and applied population genetic analysis. The exploration of DNA sequence variation for making inferences on evolutionary processes in populations requires the coordinated implementation of a Suite of Nucleotide Analysis Programs (SNAP), each bound by specific assumptions and limitations.
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