Fig. 6.

Schematic of putative role of LMO4 in cisplatin ototoxicity. The schematic illustrates the collective findings of current as well as prior studies. a) Under physiological conditions LMO4 defends the cells from apoptotic stimuli via JAK/STAT mediated activation of anti-apoptotic genes thereby facilitating cell survival. b) Cisplatin treatment induces oxidative stress by activating NOX3, which eventually leads to the nitration of LMO4 and decreases its level in the cochlea. Because LMO4 acts as a scaffold for protein complexes (e.g., glycoprotein 130), the cisplatin-induced decrease in LMO4 probably destabilizes such protein complexes, which in turn compromises the STAT3-regulated anti-apoptotic machinery. The numbers in parenthesis refer to cited publications containing corresponding data that support the link between LMO4 and other signaling molecules/pathways represented in the schematic.