{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T06:47:50Z","timestamp":1772261270062,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T00:00:00Z","timestamp":1624924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["UMO-2016\/22\/E\/NZ4\/00650"],"award-info":[{"award-number":["UMO-2016\/22\/E\/NZ4\/00650"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["UMO-2014\/13\/B\/NZ4\/00199"],"award-info":[{"award-number":["UMO-2014\/13\/B\/NZ4\/00199"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004742","name":"National Academy of Sciences of Ukraine","doi-asserted-by":"publisher","award":["0118U007352"],"award-info":[{"award-number":["0118U007352"]}],"id":[{"id":"10.13039\/501100004742","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004742","name":"National Academy of Sciences of Ukraine","doi-asserted-by":"publisher","award":["N40\/2015-2020"],"award-info":[{"award-number":["N40\/2015-2020"]}],"id":[{"id":"10.13039\/501100004742","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Glutathione (GSH) is essential for antioxidant defence, and its depletion is associated with tissue damage during cardiac ischemia-reperfusion (I\/R). GSH is synthesized by the glutamate-cysteine ligase enzyme (GCL) from L-cysteine, which alternatively might be used for hydrogen sulfide production by cystathionine-gamma-lyase (CSE). Here, we have investigated whether in vivo treatment with L-cysteine and an inhibitor of CSE,D,L-propargylglycine (PAG), can modulate cardiac glutathione and whether this treatment can influence heart resistance to I\/R in a Langendorff isolated rat hearts model. Pretreatment with PAG + L-cysteine manifested in pronounced cardioprotection, as there was complete recovery of contractile function; preserved constitutive NOS activity; and limited the production of reactive oxygen and nitrogen species in the ischemized myocardium. Cardiac GSH and GSSG levels were increased by 3.5- and 2.1-fold in PAG + L-cysteine hearts and were 3.3- and 3.6-fold higher in PAG + L-cysteine + I\/R compared to I\/R heart. The cardioprotective effect of PAG + L-cysteine was completely abolished by an inhibitor of GCL, DL-buthionine-(S,R)-sulfoximine. Further analysis indicated diminished fatty acid \u03b2-oxidation, increased glucose consumption and anaerobic glycolysis, and promoted OXPHOS proteins and SERCA2 in PAG + L-cysteine + I\/R compared to the I\/R group. PAG + L-cysteine inhibited PPAR\u03b1 and up-regulated AMPK signalling in the heart. Thus, induction of glutathione synthesis provided cardioprotection regulating NO, AMPK and PPARa signaling in ischemic rat hearts.<\/jats:p>","DOI":"10.3390\/life11070631","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T10:52:46Z","timestamp":1624963966000},"page":"631","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Induction of Glutathione Synthesis Provides Cardioprotection Regulating NO, AMPK and PPARa Signaling in Ischemic Rat Hearts"],"prefix":"10.3390","volume":"11","author":[{"given":"Yulia V.","family":"Goshovska","sequence":"first","affiliation":[{"name":"Department of Blood Circulation, Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, 4 Bogomolets Str., 01024 Kyiv, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raisa A.","family":"Fedichkina","sequence":"additional","affiliation":[{"name":"Department of Blood Circulation, Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, 4 Bogomolets Str., 01024 Kyiv, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9893-3049","authenticated-orcid":false,"given":"Volodymyr V.","family":"Balatskyi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Medical Biochemistry, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Str., 02-093 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oksana O.","family":"Piven","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150 Akad. Zabolotnogo Str., 03680 Kyiv, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pawel","family":"Dobrzyn","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Medical Biochemistry, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Str., 02-093 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vadym F.","family":"Sagach","sequence":"additional","affiliation":[{"name":"Department of Blood Circulation, Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, 4 Bogomolets Str., 01024 Kyiv, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e224","DOI":"10.1038\/emm.2016.16","article-title":"AMPK Activators: Mechanisms of Action and Physiological Activities","volume":"48","author":"Kim","year":"2016","journal-title":"Exp. 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