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Hydrogen Sulfide ameliorates mitochondrial MMP‐9 mediated mitochondria remodeling in cerebral ischemia
Author(s) -
Tyagi Neetu,
Qipshidze Natia,
Munjal Charu,
Metreveli Naria,
Dankowski Aygul,
Mishra Paras Kumar,
Sen Utpal,
Lominadze David,
Givvimani Srikanth,
Tyagi Suresh C
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.650.7
Mitophagy is strongly implicated in stroke. Hydrogen Sulfide (H 2 S), an endogenous gaseous molecule, with antioxidant activities. Therefore objective of this study was to determine whether H 2 S ameliorates mitophagy in cerebral ischemia (CI) by reducing matrix metalloproteinase‐9 (MMP‐9). There weresix groups of mice: WT, WT/CI, WT/CI+ H2S, MMP‐9 knockout(KO), MMP‐9KO/CI and MMP‐9KO/CI++ H 2 S. CI was performed for45 mins. After 2hours of injury, mice were injected with NaHS (30μM/L, H 2 S donor) for 1week. The infarct area was measured using TTC staining. Permeability was determined by brain edema and Evans Blue extravasation. PCR and Western blot were used todetermine the expression of MMP‐9, TIMPs, mitochondrial redox stress and LC3‐I/II. Mitochondrial respiratory capacity and mitochondrial permeability transition (MPT) were measured by fluorescence‐dye. The result suggested Brain edema and Evans Blue leakage were reduced after cerebral ischemia in H 2 S treated group as compared to control group along with reduced brain infarct size. Western blot analysis indicated that H 2 S decreased mitochondrial oxidativedamage and ameliorated the MMP‐9 activation and loss of MPT, in part by increasing the protein and mRNA levels of TIMP‐1 and decreasing TIMP‐2 as compared to control. This study suggests a therapeutic role of H 2 S in Cerebral Ischemia.