Gene

Kinase

Cell biology

Intracerebral hemorrhage

Biology

Calpain

Phosphoproteomics

Ubiquitin ligase

Protein phosphorylation

Signal transduction

Biochemistry

Protein kinase A

Phosphorylation

Ubiquitin

Downregulation and upregulation

Phosphatase

Bioinformatics

Enzyme

Internal medicine

Quantitative proteomics

Medicine

Proteomics

Subarachnoid hemorrhage

Journal of Molecular Neuroscience

Intracerebral hemorrhage (ICH) is a non-traumatic cerebrovascular disorder with very high morbidity and mortality and regarded as one of the deadliest stroke subtypes. Notably, there is no effective treatment for ICH. Despite an overall increase in preclinical studies, the pathophysiology of ICH is complex and remains enigmatic. To this end, ICH was induced in male CD-1 mice and the ipsilateral brain tissue was characterized in an unbiased manner using a combination of proteomics and bioinformatics approaches. A total of 4833 proteins were revealed by quantitative proteomic analysis. Of those, 207 proteins exhibited significantly altered expression after ICH in comparison to sham. It was found that 46 proteins were significantly upregulated and 161 proteins were significantly downregulated after ICH compared to sham. The quantitative proteomics approach combined with bioinformatics revealed several novel molecular targets (cyclin-dependent-like kinase 5, E3 ubiquitin-protein ligase, protein phosphatase 2A-alpha, protein phosphatase 2A-beta, serine/threonine-protein kinase PAK1, alpha-actinin-4, calpain-8, axin-1, NCK1, and septin-4), and related signaling pathways, which could play roles in secondary brain injury and long-term neurobehavioral outcomes after ICH warranting further investigation.

A Combined Proteomics and Bioinformatics Approach Reveals Novel Signaling Pathways and Molecular Targets After Intracerebral Hemorrhage