{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:51:24Z","timestamp":1790193084383,"version":"4.1.0"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2012,9,28]]},"abstract":"<jats:sec>\n                    <jats:title>\n                      <jats:underline>Rationale:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      In the myocardium, redox\/cysteine modification of proteins regulating Ca\n                      <jats:sup>2+<\/jats:sup>\n                      cycling can affect contraction and may have therapeutic value. Nitroxyl (HNO), the one-electron-reduced form of nitric oxide, enhances cardiac function in a manner that suggests reversible cysteine modifications of the contractile machinery.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Objective:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>To determine the effects of HNO modification in cardiac myofilament proteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Methods and Results:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      The HNO-donor, 1-nitrosocyclohexyl acetate, was found to act directly on the myofilament proteins, increasing maximum force (F\n                      <jats:sub>max<\/jats:sub>\n                      ) and reducing the concentration of Ca\n                      <jats:sup>2+<\/jats:sup>\n                      for 50% activation (Ca\n                      <jats:sub>50<\/jats:sub>\n                      ) in intact and skinned cardiac muscles. The effects of 1-nitrosocyclohexyl acetate are reversible by reducing agents and distinct from those of another HNO donor, Angeli salt, which was previously reported to increase F\n                      <jats:sub>max<\/jats:sub>\n                      without affecting Ca50. Using a new mass spectrometry capture technique based on the biotin switch assay, we identified and characterized the formation by HNO of a disulfide-linked actin\u2013tropomyosin and myosin heavy chain\u2013myosin light chain 1. Comparison of the 1-nitrosocyclohexyl acetate and Angeli salt effects with the modifications induced by each donor indicated the actin\u2013tropomyosin and myosin heavy chain\u2013myosin light chain 1 interactions independently correlated with increased Ca\n                      <jats:sup>2+<\/jats:sup>\n                      sensitivity and force generation, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Conclusions:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      HNO exerts a direct effect on cardiac myofilament proteins increasing myofilament Ca\n                      <jats:sup>2+<\/jats:sup>\n                      responsiveness by promoting disulfide bond formation between critical cysteine residues. These findings indicate a novel, redox-based modulation of the contractile apparatus, which positively impacts myocardial function, providing further mechanistic insight for HNO as a therapeutic agent.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.112.270827","type":"journal-article","created":{"date-parts":[[2012,8,1]],"date-time":"2012-08-01T01:55:20Z","timestamp":1343786120000},"page":"1002-1011","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":112,"title":["Nitroxyl-Mediated Disulfide Bond Formation Between Cardiac Myofilament Cysteines Enhances Contractile Function"],"prefix":"10.1161","volume":"111","author":[{"given":"Wei Dong","family":"Gao","sequence":"first","affiliation":[{"name":"From the Department of Anesthesiology and Critical Care Medicine (W.D.G., Y.T., X.Z., X.S.), Department of Biological Chemistry (C.I.M., J.E.V.E.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Pathophysiology (Y.T., X.Z.), Harbin Medical University, Harbin, China; Department of Chemistry (J.F.D., S.B.K.), Wake Forest University, Winston-Salem, NC; Division of Cardiology (B.A.S., D.B.F., J.E.V.E., N.P.), Department of Medicine, Johns Hopkins School of Medicine; Baltimore,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher I.","family":"Murray","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesiology and Critical Care Medicine (W.D.G., Y.T., X.Z., X.S.), Department of Biological Chemistry (C.I.M., J.E.V.E.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Pathophysiology (Y.T., X.Z.), Harbin Medical University, Harbin, China; Department of Chemistry (J.F.D., S.B.K.), Wake Forest University, Winston-Salem, NC; Division of Cardiology (B.A.S., D.B.F., J.E.V.E., N.P.), Department of Medicine, Johns Hopkins School of Medicine; Baltimore,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Tian","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesiology and Critical Care Medicine (W.D.G., Y.T., X.Z., X.S.), Department of Biological Chemistry (C.I.M., J.E.V.E.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Pathophysiology (Y.T., X.Z.), Harbin Medical University, Harbin, China; Department of Chemistry (J.F.D., S.B.K.), Wake Forest University, Winston-Salem, NC; Division of Cardiology (B.A.S., D.B.F., J.E.V.E., N.P.), Department of Medicine, Johns Hopkins School of Medicine; Baltimore,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhong","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesiology and Critical Care Medicine (W.D.G., Y.T., X.Z., X.S.), Department of Biological Chemistry (C.I.M., J.E.V.E.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Pathophysiology (Y.T., X.Z.), Harbin Medical University, Harbin, China; Department of Chemistry (J.F.D., S.B.K.), Wake Forest University, Winston-Salem, NC; Division of Cardiology (B.A.S., D.B.F., J.E.V.E., N.P.), Department of Medicine, Johns Hopkins School of Medicine; Baltimore,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna F.","family":"DuMond","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesiology and Critical Care Medicine (W.D.G., Y.T., X.Z., X.S.), Department of Biological Chemistry (C.I.M., J.E.V.E.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Pathophysiology (Y.T., X.Z.), Harbin Medical University, Harbin, China; Department of Chemistry (J.F.D., S.B.K.), Wake Forest University, Winston-Salem, NC; Division of Cardiology (B.A.S., D.B.F., J.E.V.E., N.P.), Department of Medicine, Johns Hopkins School of Medicine; Baltimore,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxu","family":"Shen","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesiology and Critical Care Medicine (W.D.G., Y.T., X.Z., X.S.), Department of Biological Chemistry (C.I.M., J.E.V.E.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Pathophysiology (Y.T., X.Z.), Harbin Medical University, Harbin, China; Department of Chemistry (J.F.D., S.B.K.), Wake Forest University, Winston-Salem, NC; Division of Cardiology (B.A.S., D.B.F., J.E.V.E., N.P.), Department of Medicine, Johns Hopkins School of Medicine; Baltimore,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian A.","family":"Stanley","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesiology and Critical Care Medicine (W.D.G., Y.T., X.Z., X.S.), Department of Biological Chemistry (C.I.M., J.E.V.E.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Pathophysiology (Y.T., X.Z.), Harbin Medical University, Harbin, China; Department of Chemistry (J.F.D., S.B.K.), Wake Forest University, Winston-Salem, NC; Division of Cardiology (B.A.S., D.B.F., J.E.V.E., N.P.), Department of Medicine, Johns Hopkins School of Medicine; Baltimore,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Brian","family":"Foster","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesiology and Critical Care Medicine (W.D.G., Y.T., X.Z., X.S.), Department of Biological Chemistry (C.I.M., J.E.V.E.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Pathophysiology (Y.T., X.Z.), Harbin Medical University, Harbin, China; Department of Chemistry (J.F.D., S.B.K.), Wake Forest University, Winston-Salem, NC; Division of Cardiology (B.A.S., D.B.F., J.E.V.E., N.P.), Department of Medicine, Johns Hopkins School of Medicine; Baltimore,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Wink","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesiology and Critical Care Medicine (W.D.G., Y.T., X.Z., X.S.), Department of Biological Chemistry (C.I.M., J.E.V.E.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Pathophysiology (Y.T., X.Z.), Harbin Medical University, Harbin, China; Department of Chemistry (J.F.D., S.B.K.), Wake Forest University, Winston-Salem, NC; Division of Cardiology (B.A.S., D.B.F., J.E.V.E., N.P.), Department of Medicine, Johns Hopkins School of Medicine; Baltimore,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Bruce","family":"King","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesiology and Critical Care Medicine (W.D.G., Y.T., X.Z., X.S.), Department of Biological Chemistry (C.I.M., J.E.V.E.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Pathophysiology (Y.T., X.Z.), Harbin Medical University, Harbin, China; Department of Chemistry (J.F.D., S.B.K.), Wake Forest University, Winston-Salem, NC; Division of Cardiology (B.A.S., D.B.F., J.E.V.E., N.P.), Department of Medicine, Johns Hopkins School of Medicine; Baltimore,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer E.","family":"Van Eyk","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesiology and Critical Care Medicine (W.D.G., Y.T., X.Z., X.S.), Department of Biological Chemistry (C.I.M., J.E.V.E.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Pathophysiology (Y.T., X.Z.), Harbin Medical University, Harbin, China; Department of Chemistry (J.F.D., S.B.K.), Wake Forest University, Winston-Salem, NC; Division of Cardiology (B.A.S., D.B.F., J.E.V.E., N.P.), Department of Medicine, Johns Hopkins School of Medicine; Baltimore,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazareno","family":"Paolocci","sequence":"additional","affiliation":[{"name":"From the Department of Anesthesiology and Critical Care Medicine (W.D.G., Y.T., X.Z., X.S.), Department of Biological Chemistry (C.I.M., J.E.V.E.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Pathophysiology (Y.T., X.Z.), Harbin Medical University, Harbin, China; Department of Chemistry (J.F.D., S.B.K.), Wake Forest University, Winston-Salem, NC; Division of Cardiology (B.A.S., D.B.F., J.E.V.E., N.P.), Department of Medicine, Johns Hopkins School of Medicine; Baltimore,..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06798"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2000.80.2.853"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr026"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.105.542407"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.7.3892"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1044503"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1144318"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3859"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.2174\/092986709789712880"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2007.1886"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.70.6.1217"},{"key":"e_1_3_5_13_2","first-page":"845","article-title":"Oxygen radicals attenuate the contractility of skinned muscle fibres from the pig myocardium.","volume":"49","author":"Lowe H","year":"1994","unstructured":"Lowe H, Baeger I, Blasig IE, Haseloff RF. 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