Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:6.3.2.19 (
ubiquitin-protein ligase
)
799
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Subarachnoid hemorrhage (SAH), mostly caused by aneurysm rupture, is a pathological condition associated with oxidative stress and neuroinflammation. Toll-like receptors (TLRs) are a family of key regulators of neuroinflammation, and
RNF216
is an E3
ubiquitin-protein ligase
that regulates TLRs via ubiquitination and proteolytic degradation. However, the role of
RNF216
in SAH has not been determined. In this study, we investigated the biological function of
RNF216
in experimental SAH models both in vitro and in vivo. The expression of
RNF216
was found to be upregulated in cortical neurons after oxyhemoglobin (OxyHb) treatment, and increased
RNF216
expression was also observed in brain tissues in the single-hemorrhage model of SAH. Downregulation of
RNF216
expression by short interfering RNA (siRNA) transfection significantly reduced cytotoxicity and apoptosis after OxyHb exposure. The results of western blot showed that the
RNF216
-mediated neuronal injury in vitro was associated with the regulation of the Arc-AMPAR pathway, which was related to intracellular Ca
2+
dysfunction, as evidenced by Ca
2+
imaging. In addition, knockdown of
RNF216
in vivo using intraventricular injection of siRNA was found to attenuate brain injury and neuroinflammation via the Arc-AMPAR pathway after SAH in the animal model. In summary, we demonstrated that silence of
RNF216
expression protects against neuronal injury and neurological dysfunction in experimental SAH models. These data support for the first time that
RNF216
may represent a novel candidate for therapies against SAH.
...
PMID:RNF216 mediates neuronal injury following experimental subarachnoid hemorrhage through the Arc/Arg3.1-AMPAR pathway. 3291 71
