Back to Search
Start Over
Molecular Mechanism Underlying Hypoxic Preconditioning-Promoted Mitochondrial Translocation of DJ-1 in Hypoxia/Reoxygenation H9c2 Cells.
- Source :
-
Molecules (Basel, Switzerland) [Molecules] 2019 Dec 24; Vol. 25 (1). Date of Electronic Publication: 2019 Dec 24. - Publication Year :
- 2019
-
Abstract
- DJ-1 was recently reported to be involved in the cardioprotection of hypoxic preconditioning (HPC) against hypoxia/reoxygenation (H/R)-induced oxidative stress damage, by preserving mitochondrial complex I activity and, subsequently, inhibiting mitochondrial reactive oxygen species (ROS) generation. However, the molecular mechanism by which HPC enables mitochondrial translocation of DJ-1, which has no mitochondria-targeting sequence, to preserve mitochondrial complex I, is largely unknown. In this study, co-immunoprecipitation data showed that DJ-1 was associated with glucose-regulated protein 75 (Grp75), and this association was significantly enhanced after HPC. Immunofluorescence imaging and Western blot analysis showed that HPC substantially enhanced the translocation of DJ-1 from cytosol to mitochondria in H9c2 cells subjected to H/R, which was mimicked by DJ-1 overexpression induced by pFlag-DJ-1 transfection. Importantly, knockdown of Grp75 markedly reduced the mitochondrial translocation of DJ-1 induced by HPC and pFlag-DJ-1 transfection. Moreover, HPC promoted the association of DJ-1 with mitochondrial complex I subunits ND1 and NDUFA4, improved complex I activity, and inhibited mitochondria-derived ROS production and subsequent oxidative stress damage after H/R, which was also mimicked by pFlag-DJ-1 transfection. Intriguingly, these effects of HPC and pFlag-DJ-1 transfection were also prevented by Grp75 knockdown. In conclusion, these results indicated that HPC promotes the translocation of DJ-1 from cytosol to mitochondria in a Grp75-dependent manner and Grp75 is required for DJ-1-mediated protection of HPC on H/R-induced mitochondrial complex I defect and subsequent oxidative stress damage.
- Subjects :
- Animals
Cardiotonic Agents metabolism
Cell Line
HSP70 Heat-Shock Proteins metabolism
Mitochondrial Proteins metabolism
Oxidative Stress
Protein Binding
Protein Transport
Rats
Reactive Oxygen Species metabolism
Hypoxia metabolism
Mitochondria metabolism
Myocytes, Cardiac metabolism
Oxygen metabolism
Protein Deglycase DJ-1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1420-3049
- Volume :
- 25
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecules (Basel, Switzerland)
- Publication Type :
- Academic Journal
- Accession number :
- 31878239
- Full Text :
- https://doi.org/10.3390/molecules25010071