Testosterone protects cardiac myocytes from superoxide injury via NF-κB signalling pathways

Fu Ying Xiao, Lina Nheu, Paul Komesaroff, Shanhong Ling

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26 Citations (Scopus)


Aims Cellular and molecular mechanisms underlying the effects of androgenic hormone testosterone on the heart remain unclear. This study examined the impact of testosterone on viability of cardiac myocytes and the role of NF-κB signalling pathways. Materials and methods Rat H9c2 myocytes were cultured in steroid-free media and incubated with hydrogen peroxide (H2O2, 200 μM, 6 h). NF-κB expression was knocked down by RelA (p65) siRNA interference. Testosterone (5-100 nM, 24-48 h) was provided into the media and androgen receptor (AR) blocked by flutamide (100 nM). Cell apoptotic/necrotic death was determined by morphological examination and flow-cytometric analysis. Gene expression was examined by Western blotting analysis. Key findings Testosterone supplements reduced the superoxide-induced apoptotic/necrotic death, stimulated NF-κB (RelA) expression, activated Akt activity, and inhibited Caspase-3 expression in the cardiac myocytes. The hormonal effects were abolished by either AR blocker flutamide or NF-κB-knockdown. Testosterone also induced ERK1/2 activation, which was not affected by flutamide or NF-κB knockdown, and blocking the ERK activity did not affect the protective effect of the hormone on the cells. Significance This study demonstrates that exogenous testosterone supplementation protects cardiac myocytes from superoxide injury via AR mediation and dependent on normally functional canonical NF-κB (RelA/p50) signalling pathways. The NF-κB signalling may be an important key molecular basis for myocardial benefits of hormone (testosterone) therapy.

Original languageEnglish
Pages (from-to)45-52
Number of pages8
JournalLife Sciences
Publication statusPublished - 4 Jun 2015


  • Androgen receptor (AR)
  • Cardiac myocytes
  • Nuclear factor-κB (NF-κB)
  • Superoxide injury
  • Testosterone

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