科研之友
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摘要
Hydrogen sulfide (H2S) is a novel neurotransmitter. We studied here the effect of ACS 84, a new H2S releasing compound, on the cytotoxicity induced by amyloid beta (A beta) in microglia. Treatment with A beta(1-40) (25 mu mol/L) for 24 h significantly inhibited MTT reduction and increased lactate dehydrogenase release in BV-2 microglia cells. Pretreatment with ACS 84 (10 mu M) for 30 min attenuated the above cytotoxicity caused by A beta(1-40), suggesting that ACS 84 may protect microglia against A beta(1-40)-induced cell injury. ACS 84 also significantly attenuated nitric oxide release and TNF-alpha production in BV-2 cells treated with A beta peptides (A beta(1-40) or A beta(1-42)), but had no significant effect on the up-regulated protein expression of cyclooxygenase 2. These data suggest that ACS 84 may produce anti-inflammatory effect via inhibition of the release of inflammatory cytokines but not via suppression of the prostanoids production. Furthermore, pretreatment with ACS 84 also attenuated mitochondrial membrane potential loss (Delta psi m) caused by A beta(1-40) in both microglia and neurons. To examine the underlying signaling mechanism, we detected the phosphorylation of p38-, JNK- and ERK-MAPKs. It was found that A beta(1-40) stimulated phosphorylation of all above three types of MAKPs. However, ACS 84 only attenuated the activation of p38 and JNK, but had no significant effect on that of ERK. Taken together, our data suggest that ACS 84 may protect A beta-induced cell injury via anti-inflammation and preservation of mitochondrial function in a p38 and JNK dependent mechanism. Our work suggests that ACS 84 may have potential for the treatment of neurodegenerative diseases.
- 出版日期2011-4
