Quantitative Proteomics Characterization of the Effect and Mechanism of Trichostatin A on the Hippocampus of Type II Diabetic Mice

by Selleckchem | Jan 03 2024

Diabetic encephalopathy (DE) is one of the complications of diabetes mellitus with mild-to-moderate cognitive impairment. Trichostatin A (TSA) has been revealed to show protective effect on central nervous systems in Alzheimer's disease (AD) and hypoxic-ischemic brain injury. However, the effect and molecular mechanism of TSA on cognitive function of DE are unknown. Here, we demonstrated that cognitive function was damaged in diabetic mice versus normal mice and treatment with TSA improved cognitive function in diabetic mice. Proteomic analysis of the hippocampus revealed 174 differentially expressed proteins in diabetic mice compared with normal mice. TSA treatment reversed the expression levels of 111 differentially expressed proteins grouped into functional clusters, including the longevity regulating pathway, the insulin signaling pathway, peroxisomes, protein processing in the endoplasmic reticulum, and ribosomes. Furthermore, protein-protein interaction network analysis of TSA-reversed proteins revealed that UBA52, CAT, RPL29, RPL35A, CANX, RPL37, and PRKAA2 were the main hub proteins. Multiple KEGG pathway-enriched CAT and PRKAA2 levels were significantly decreased in the hippocampus of diabetic mice versus normal mice, which was reversed by TSA administration. Finally, screening for potential similar or ancillary drugs for TSA treatment indicated that HDAC inhibitors ISOX, apicidin, and panobinostat were the most promising similar drugs, and the PI3K inhibitor GSK-1059615, the Aurora kinase inhibitor alisertib, and the nucleophosmin inhibitor avrainvillamide-analog-6 were the most promising ancillary drugs. In conclusion, our study revealed that CAT and PRKAA2 were the key proteins involved in the improvement of DE after TSA treatment. ISOX, apicidin, and panobinostat were promising similar drugs and that GSK-1059615, alisertib, and avrainvillamide-analog-6 were promising ancillary drugs to TSA in the treatment of DE.

Comments:

This research you've shared highlights the potential therapeutic role of Trichostatin A (TSA) in addressing cognitive impairment associated with diabetic encephalopathy (DE) in mice. It's fascinating how TSA appears to improve cognitive function in diabetic mice and its impact on differentially expressed proteins in the hippocampus.

The findings suggest that TSA treatment:

1. Improved cognitive function in diabetic mice.
2. Reversed the expression levels of several proteins in functional clusters related to pathways like longevity regulation, insulin signaling, peroxisomes, protein processing in the endoplasmic reticulum, and ribosomes.
3. Identified specific hub proteins (UBA52, CAT, RPL29, RPL35A, CANX, RPL37, and PRKAA2) affected by TSA treatment.
4. Showed a significant reversal of CAT and PRKAA2 levels affected by diabetes and restored by TSA administration.
5. Suggested potential similar (HDAC inhibitors like ISOX, apicidin, and panobinostat) and ancillary drugs (PI3K inhibitor GSK-1059615, Aurora kinase inhibitor alisertib, nucleophosmin inhibitor avrainvillamide-analog-6) for TSA treatment in DE.

The identification of CAT and PRKAA2 as key proteins influenced by TSA treatment and the exploration of potential similar or ancillary drugs for TSA in DE treatment provide promising insights for further research and potential therapeutic interventions.

This kind of study can pave the way for targeted treatments and further investigation into the molecular mechanisms underlying DE and its management. Understanding how TSA influences these pathways and proteins could lead to more targeted and effective therapies for cognitive impairment in diabetic individuals.