Research ReportInhibition of SENP3 by lentivirus induces suppression of apoptosis in experimental subarachnoid hemorrhage in rats

highlights
- To our knowledge, this is the first study to reveal the role of SENP3 in the brain after SAH.
- It is found that high oxidative stress level following SAH induced rising of SENP3.
- Increased apoptosis caused by SENP3 accumulation may be a major reason for neural death after SAH.

BackgroundSubarachnoid hemorrhage (SAH) is one of the life-threatening diseases with high morbidity and mortality rates. SUMO-specific proteases 3 (SENP3), a member of the small ubiquitin-like modifier specific protease family, was identified as an isopeptidase that deconjugates SUMOylation (The covalent modification by SUMO) of modified protein substrates. It is reported that SUMO-2/3 conjugation, a member of SUMOylation, presented neuroprotection. The study aimed to evaluate the expression of SENP3 and to explore its potential role in SAH.Materials and methodsA total of 108 Sprague Dawley (SD) rats were randomly divided into 2 parts experiment and 9 subgroups (part 1:Sham group, SAH group, SAH+NAC group, SAH+vehicle group; part 2: Sham group, SAH group, SAH+lv-SENP3 group, SAH+lv-null group, SAH+NS group). 7 days before SAH, lentivirus was administrated into rats׳ left lateral ventricle to down-regulate SENP3. Experimental SAH was imitated by injection with 0.3 ml nonheparinized autoblood into the prechiasmatic cistern. MDA levels, SOD activities, and GSH contents were detected to evaluate oxidative stress level. SENP3 and cleaved caspase 3 were detected by western blot, apoptosis was observed by TUNEL staining.ResultsHigh oxidative stress level following SAH induced rising of SENP3. And inhibition of SENP3 by lentivirus induces suppression of apoptosis in experimental subarachnoid hemorrhage in rats.ConclusionWhen SENP3 accumulated by high oxidative stress, caspase 3 activated subsequently. And it leads to more severe apoptosis than physiological.