体外研究: |
TA-02 (5 μM) inhibits the phosphorylation of proteins downstream of p38α MAPK such as MAPKAPK2 and HSP27 during cardiogenesis. TA-02 at 5 μM concentration induces cardiogenesis, but also increases ATF-2 phosphorylation and MEF2C õexpression in contrast to what would be expected with a mechanism dependent on p38α MAPK inhibition. TA-02 induces T/Brachyury whereas SB203580 addition increased MESP1 and T/Brachyury transcripts. TA-02 significantly induces high NKX2-5 expression when applied between days 0-8. TA-02 is found to inhibit multiple targets with similar potency to p38α MAPK, such as p38α, p38β, JNK3, JNK2, CIT, CK1ε, DMPK2, JNK1, DDR1 CK1δ, MEK5, and ERBB2. TA-02 and SB203580 reduce the nuclear TCF/LEF-1 driven transcription of luciferase similar to DKK-1.TA-02 (5 nM-5 μM) inhibits p38 and increases the anti-inflammation effects of BDNF on inflammation in vitro. Western Blot Analysis Cell Line: The nerve cell line AGE1.HN. Concentration: 5 nM-5 μM. Incubation Time: 44 h (100 ng/ml LPS for 4 h at 37°C). Result: Suppressed p-38 protein expression, reduced IL-1β, IL-6, IL-18 and TNF-α levels and inhibited iNOS and COX-2 levels in an in vitro model of SCI by BDNF overexpression, compared with the BDNF overexpression group. |