Increased Expression of Ubiquitin-Specific Protease 4 Participates in Neuronal Apoptosis After Intracerebral Hemorrhage in Adult Rats.
Ubiquitinating enzymes catalyze protein ubiquitination, a reversible process countered by deubiquitinating enzyme (DUB) action. Ubiquitin-specific protease 4 (USP4) is a member of the ubiquitin-specific protease (USP) family of DUBs that has a role in spliceosome regulation. In the present study, we demonstrated that USP4 may be involved in neuronal apoptosis in the processes of intracerebral hemorrhage (ICH). We obtained a significant up-regulation of USP4 in neurons adjacent to the hematoma following ICH by the results of Western blot, immunohistochemistry, and immunofluorescence. Increasing USP4 level was found to be accompanied by the up-regulation of active caspase-3, γH2AX, Bax, and decreased expression of Bcl-2. In addition, USP4 co-localized well with γH2AX in the nucleus in the ICH model and hemin-induced apoptosis model. Moreover, in vitro study, knocking down USP4 by USP4-specific siRNA in PC12 cells reduced active caspase-3 expression. All these results above suggested that USP4 may be involved in neuronal apoptosis after ICH.
Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, 226001, Jiangsu, China.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, Jiangsu, China.
Chao
C
Liu
Laboratory Animal Center, Nantong University, Nantong, 226001, Jiangsu, China.
Chun
C
Liu
Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, 226001, Jiangsu, China.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, Jiangsu, China.
Hanzhang
H
Liu
Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, 226001, Jiangsu, China.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, Jiangsu, China.
Leilei
L
Gong
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, 226001, Jiangsu, China.
Tao
T
Tao
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, 226001, Jiangsu, China.
Yifen
Y
Shen
Laboratory Animal Center, Nantong University, Nantong, 226001, Jiangsu, China. zhushunxingnt@126.com.
Shunxing
S
Zhu
Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, 226001, Jiangsu, China. shenaiguont@126.com.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, Jiangsu, China. shenaiguont@126.com.
Aiguo
A
Shen
D000375:Aging / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000201:enzymology* / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D008297:Male; D009474:Neurons / Q000201:enzymology* / Q000473:pathology*; D010641:Phenotype; D017207:Rats, Sprague-Dawley; D044767:Ubiquitin-Protein Ligases; D064570:Ubiquitin-Specific Proteases / Q000378:metabolism*
D015415:Biomarkers; D044767:Ubiquitin-Protein Ligases; D064570:Ubiquitin-Specific Proteases; C000615623:Usp4 protein, rat
Adult rats; Intracerebral hemorrhage; Neuronal apoptosis; USP4