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jdk.nashorn.api.scripting.NashornScriptEngine.getInterface(java.lang.Object,java.lang.Class) public java.lang.Object jdk.nashorn.api.scripting.NashornScriptEngine.getInterface(java.lang.Class) public java.lang.Object jdk.nashorn.api.scripting.NashornScriptEngine.invokeMethod(java.lang.Object,java.lang.String,java.lang.Object[]) throws javax.script.ScriptException,java.lang.NoSuchMethodException public java.lang.Object jdk.nashorn.api.scripting.NashornScriptEngine.invokeFunction(java.lang.String,java.lang.Object[]) throws javax.script.ScriptException,java.lang.NoSuchMethodException public javax.script.Bindings jdk.nashorn.api.scripting.NashornScriptEngine.createBindings() public java.lang.Object javax.script.AbstractScriptEngine.get(java.lang.String) public void javax.script.AbstractScriptEngine.put(java.lang.String,java.lang.Object) public javax.script.ScriptContext javax.script.AbstractScriptEngine.getContext() public java.lang.Object 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Journal of Southern Medical University ›› 2026, Vol. 46 ›› Issue (5): 1075-1083.doi: 10.12122/j.issn.1673-4254.2026.05.11

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Growth differentiation factor 11 attenuates hypoxia/reoxygenation injury in rat H9C2 cardiomyocytes in vitro by inhibiting thioredoxin-1 nitrative inactivation

Jia WEI(), Wei JIANG, Linying XIA, Lü LÜ, Qiang YANG()   

  1. Department of Cardiology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
  • Received:2025-09-26 Online:2026-05-20 Published:2026-05-27
  • Contact: Qiang YANG E-mail:308796226@qq.com;str_yq03@163.com

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Abstract:

Objective To verify the hypothesis that growth differentiation factor 11 (GDF11) attenuates myocardial ischemia/reperfusion (MI/R) injury and explore the underlying mechanism. Methods To simulate MI/R injury, H9C2 cells were incubated in an anaerobic chamber (95% N2+5% CO2) for 9 h followed by 3 h of reoxygenation in the presence of GDF11 (10 nmol/L). The cells exposed to hypoxia/reoxygenation (H/R) or sham exposure were treated with GDF11 alone or in combination with the iNOS inhibitor 1400W, the Trx1 nitration inhibitor EUK134, human recombinant Trx1 (hTrx1) or N-Trx1, and the changes in cell viability was determined by MTT assay and LDH release assay. Cardiomyocyte apoptosis was determined by TUNEL staining and caspase-3 activity assessment, and oxidative stress levels were evaluated by measuring superoxide production and DHE staining. Nitrative stress in the cells was assessed by measuring total NO content and nitrotyrosine content. The expression levels of iNOS, gp91phox, ASK1 and p-ASK1 were detected using Western blotting, Trx1 activity was determined using insulin disulfide reduction assay, and Trx1 nitration was analyzed by immunoprecipitation. Results In H9C2 cells with H/R exposure, 10 nmol/L GDF11 treatment significantly increased cell viability, decreased LDH release, inhibited caspase-3 activation and cell apoptosis, and reduced superoxide production, total NO content and nitrotyrosine production. GDF11 also significantly inhibited iNOS expression, reversed H/R-induced increase of Trx1 nitration and inhibition of Trx1 activity, and inhibited ASK1 phosphorylation. Treatment of the cells with 1400W decreased LDH release and caspase-3 activity, and diminished total NO production and nitrotyrosine production. EUK134 diminished LDH release and caspase-3 activation, upregulated Trx activity, and inhibited superoxide production in H9C2 cells. N-Trx1 abolished the protective effects of GDF11 against H/R injury in the cardiomyocytes. Conclusion GDF11 protects cardiomyocytes against H/R injury partially by attenuating oxidative/nitrative stress and inhibiting Trx1 nitrative inactivation.

Key words: growth differentiation factor 11, myocardial ischemia/reperfusion injury, oxidative/nitrative stress, thioredoxin-1 nitration, apoptosis