TRIM22-Mediated Apoptosis is Associated with Bak Oligomerization in Monocytes

Abstract

Monocyte apoptosis is a key mechanism that orchestrates host immune responses during sepsis. TRIM22 is constitutively expressed at high levels in monocytes and plays important roles in the antiviral response and inflammation. Overexpression of TRIM22 interferes with the clonogenic growth of monocytic cells, suggesting that TRIM22 may regulate monocyte survival. However, the effect of TRIM22 on monocyte apoptosis remains unknown. In the present report, lipopolysaccharides (LPS)-primed human peripheral blood monocytes expressing higher levels of TRIM22 were more sensitive to apoptosis. This phenomenon was also observed in TRIM22-overexpressing THP-1 monocytes and was associated with the activation of caspase-9 and caspase-3, as well as the increased expression and oligomerization of the pro-apoptotic protein Bak. Similar expression patterns of TRIM22 and Bak were also observed in LPS-primed, apoptotic human peripheral blood monocytes. In addition, the deletion of either the RING domain or the SPRY domain of TRIM22 significantly attenuated TRIM22-mediated monocyte apoptosis and decreased Bak expression and oligomerization. Furthermore, in monocytes from septic patients, TRIM22 levels were down-regulated and positively correlated with Bak levels. Taken together, these results indicate that TRIM22 plays a critical role in monocyte apoptosis by regulating Bak oligomerization and may have a potential function in the pathogenesis of sepsis.

Usnic Acid and Usnea barbata (L.) F.H. Wigg. Dry Extracts Promote Apoptosis and DNA Damage in Human Blood Cells through Enhancing ROS Levels

“…The resulting cycle causes a proton leak that could dissipate the proton grad across the membrane, altering ATP levels and changing mitochondrial membrane potential [ 125 ]. Usnic acid can induce structural changes in intracellular glutathione molecules, decreasing its reduced form (GSH) [ 126 ]. In the same mode, usnic acid can perform spectrin oxidation with cell membrane shrinkage and PS exposure during apoptosis.…”

Delineating Crosstalk Mechanisms of the Ubiquitin Proteasome System That Regulate Apoptosis

“…It is known that deletion of RING or SPRY domain of TRIM22 decreases the monocyte-mediated apoptosis. Mechanistic details on the Bak oligomerization mediated by TRIM22 and whether it is regulated directly or in the association of other factors need to be further explored as this would provide more understanding on monocyte-mediated apoptosis (Chen et al, 2017 ). Knockdown of WWP1 E3 ligase is associated with caspase-9 activation, cleavage of PARP and apoptosis.…”

Tripartite Motif 22 and Class II Transactivator Restriction Factors: Unveiling Their Concerted Action against Retroviruses

“…Furthermore, the B30.2/SPRY was shown to dictate the different subcellular distributions and thus specific functions of TRIM family members ( 34 , 35 ). Indeed, the B30.2/SPRY domain is essential for TRIM22-mediated activation of nuclear factor kappa B (NF-κB) ( 26 , 36 ) and possibly for the recently described TRIM22-mediated monocyte apoptosis ( 37 ). The intimate reasons of the distinct subcellular distribution of TRIM22 found in various studies, however, remain controversial.…”