Liproxstatin-1 protects the mouse myocardium against ischemia/reperfusion injury by decreasing VDAC1 levels and restoring GPX4 levels

Yansheng Feng, Ngonidzashe B. Madungwe, Abdulhafiz D. Imam Aliagan, Nathalie Tombo, Jean C. Bopassa

Resultado de la investigación: Articlerevisión exhaustiva

87 Citas (Scopus)

Resumen

Ferroptosis is a distinct iron-dependent mechanism of regulated cell death recognized in cancer and ischemia/reperfusion (I/R) injury of different organs. It has been reported that molecules such as liproxstatin-1 (Lip-1) inhibit ferroptosis and promote cell survival however, the mechanisms underlying this action are not clearly understood. We investigated the role and mechanism of Lip-1 in reducing cell death in the ischemic myocardium. Using an I/R model of isolated perfused mice hearts in which Lip-1 was given at the onset of reperfusion, we found that Lip-1 protects the heart by reducing myocardial infarct sizes and maintaining mitochondrial structural integrity and function. Further investigation revealed that Lip-1-induced cardioprotection is mediated by a reduction of VDAC1 levels and oligomerization, but not VDAC2/3. Lip-1 treatment also decreased mitochondrial reactive oxygen species production and rescued the reduction of the antioxidant GPX4 caused by I/R stress. Meanwhile, mitochondrial Ca2+ retention capacity needed to induce mitochondrial permeability transition pore opening did not change with Lip-1 treatment. Thus, we report that Lip-1 induces cardioprotective effects against I/R injury by reducing VDAC1 levels and restoring GPX4 levels.

Idioma originalEnglish (US)
Páginas (desde-hasta)606-611
Número de páginas6
PublicaciónBiochemical and Biophysical Research Communications
Volumen520
N.º3
DOI
EstadoPublished - dic. 10 2019

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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