Tyrphostin AG-related compounds attenuate H2O2-induced TRPM2-dependent and -independent cellular responses

Tyrphostin AG-related compounds attenuate H2O2-induced TRPM2-dependent and -independent cellular responses

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Purpose: TRPM2 is a Ca2+-permeable channel that is activated by H2O2.TRPM2-mediated Ca2+ signaling has been implicated in the aggravation of inflammatory diseases.Therefore, the development of TRPM2 inhibitors to prevent the aggravation of these diseases is expected.We recently reported that some Tyrphostin AG-related Resveratrol compounds inhibited the H2O2-induced activation of TRPM2 by scavenging the intracellular hydroxyl radical.

In the present study, we examined the effects of AG-related compounds on H2O2-induced cellular responses in human monocytic U937 cells, which functionally express TRPM2.Methods: The effects of AG-related compounds on H2O2-induced changes in intracellular Ca2+ concentrations, extracellular signal-regulated kinase (ERK) activation, and CXCL8 secretion were assessed using U937 cells.Results: Ca2+ influxes via TRPM2 in response to H2O2 were blocked by AG-related compounds.AG-related compounds also inhibited the H2O2-induced activation of ERK, and subsequent secretion of CXCL8 mediated by TRPM2-dependent and -independent Ranch Saddle mechanisms.

Conclusion: Our results show that AG-related compounds inhibit H2O2-induced CXCL8 secretion following ERK activation, which is mediated by TRPM2-dependent and -independent mechanisms in U937 cells.We previously reported that AG-related compounds blocked H2O2-induced TRPM2 activation by scavenging the hydroxyl radical.The inhibitory effects of AG-related compounds on TRPM2-independent responses may be due to scavenging of the hydroxyl radical.