Succinate is an inflammatory signal that induces IL-1β through HIF-1α.

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2014/06/20 咦, 有PubPeer alert呦…
Christos Chinopoulos | Jun 20 2014 05:48 EST

Could it be that LPS-induced succinate over-production is due to itaconate formation? LPS induces Irg1, a gene coding for cis-aconitate decarboxylase, specifically expressed in cells of macrophage lineage Proc Natl Acad Sci U S A. 2013 May 7;110(19):7820-5. doi: 10.1073/pnas.1218599110, yielding itaconate. Itaconate is preferentially used by succinyl CoA ligase forming itaconyl CoA, thus generating an accumulation of succinate when the ligase operates towards succinyl CoA formation ADLER J, WANG SF, & Lardy HA (1957) The metabolism of itaconic acid by liver mitochondria. J. Biol. Chem, 229, 865-879, and WANG SF, ADLER J, & Lardy HA (1961) The pathway of itaconate metabolism by liver mitochondria. J. Biol. Chem, 236, 26-30. http://www.ncbi.nlm.nih.gov/pubmed/23535595#cm23535595_4939

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2017/02/23 奕宏問了一個好問題, 抱歉, 我回來想想我當場的解釋並不正確, 現在重來一次! Orz…

Suppl Fig 15

奕宏問說, 既然IL1B是HIF1A(a transcription factor)的下游, 何以兩者的表現量未呈正相關?

我原先回答說transcript regulation level(IL1B)和protein regulation level (HIF1A)不同, 不用這樣子一起比。但是，仔細看著它們，既然細胞是一樣的，不管受什麼level調節，兩者應該要同上同下才對，因為它們的context是相同的。

因此，剩下的唯一可能應是使用diethylsuccinate(DS)和butylmalonate(BM)所造成的差異。例如，BM除了induce HIF1A stabilization以外，還有stabilize其它IL1B之上游分子，而那些因子在DS那一組並未出現。如此便可解釋為何HIF1A和IL1B在兩種藥處理下，蛋白量並未成正相關。 How do you like this idea, Yi-Hong? 😀

2017/02/23 Journal Club paper

Succinate is an inflammatory signal that induces IL-1β through HIF-1α.

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