Journal
EXPERIMENTAL CELL RESEARCH
Volume 400, Issue 1, Pages -Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2020.112437
Keywords
TRIM27; PPAR gamma; Ubiquitination; Apoptosis; Inflammation
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Funding
- Innovative research team of high-level local universities in Shanghai, National Natural Science Foundation of China [82071445, 82071341, 81771295]
- Innovative Research Team of High-level Local Universities in Shanghai, Natural Science Foundation of Shanghai [15ZR1412900]
- Shanghai Jiaotong University Medical Engineering Foundation [YG2015MS52]
- Epilepsy Research Foundation of the China Association Against Epilepsy [2014004]
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The study suggests that TRIM27 mediates ubiquitination of PPAR gamma, leading to increased expression of cleaved Caspase-3 and IL-1 beta, promoting Glu-induced apoptosis and IL-1 beta release in HT22 cells.
Neurotoxicity induced by glutamate (Glu) is often used to study the signaling mechanism of neurological disorders. The identification of specific genetic factors that cause Glu-induced neurotoxicity provides evidence for the common pathways of neuronal apoptosis and inflammation. TRIM27 has been found to induce apoptosis and inflammation. Nevertheless, there is little evidence that TRIM27 is associated with Glu-induced neurotoxicity. We found that TRIM27 expression was increased in epilepsy patients and in HT22 cells following Glu treatment. Glu-mediated cell apoptosis, decreased PPAR gamma expression, and increased levels of cleaved Caspase-3 and IL-1 beta expression in HT22 cells were significantly inhibited by TRIM27 knockdown. TRIM27 overexpression significantly induced cell apoptosis and expression of cleaved Caspase-3 and IL-1 beta, but inhibited PPAR gamma expression in HT22 cells, which were reversed by ROZ, suggesting the involvement of PPAR gamma in TRIM27-mediated cell apoptosis and inflammation in HT22 cells. Mechanically, TRIM27 ubiquitinates and degrades PPAR gamma, following induces cleaved Caspase-3 and IL-1 beta expression. Clinically, increased expression of TRIM27 in epilepsy patients was associated with decreased PPAR gamma expression. Taken together, our study suggests that TRIM27-mediated ubiquitination of PPAR gamma promotes Glu-induced HT22 cell apoptosis and IL-1 beta release.
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