Omi/HtrA2 is a mammalian serine protease and has high homology to bacterial HtrA chaperones. This protease exhibits in mitochondria. And Omi also acts as a mitochondrial protein and it releases to the cytoplasm after apoptotic stimuli.

Omi protein is synthesized as a precursor that is processed in the mitochondria to produce the mature protein. Processing of the precursor Omi polypeptide is an intramolecular reaction. As a result, Omi acts as a mitochondrial protein and it releases to the cytoplasm after apoptotic stimuli. This protein also induces apoptosis in a caspase-independent manner. However, the clear mechanism or function of Omi is clearly understood.

In this article, we will introduce a specific Omi/HtrA2 inhibitor, Ucf-101.

Ucf-101 is a selective and competitive inhibitor of pro-apoptotic protease Omi/HtrA2, with an IC50 of 9.5 μM for His-Omi. Ucf-101 exhibits very little activity against various other serine proteases (IC50>200 μM).
This compound has a natural red fluorescence at 543 nm and can be used to monitor its ability to enter mammalian cells.

Ucf-101 (1-20 μM; pretreated for 1 h) inhibits the 6-OHDA-induced apoptosis of Parkinson’s disease (PD)-PC12 cells at the low concentration (2.5 μM), And it increases the apoptosis rate at the high concentration (≥10 μM).  Furthermore, in PD-PC12 cells, 6-OHDA upregulates the expression of HtrA2, α-syn, Grp78, and active caspase-3. But Ucf-101 down-regulates the expression of Glucose-regulated protein 78 (Bip/Grp78) and C/EBP homologous protein (CHOP). Additionally, At the same time, it reduces the levels of TH and XIAP. Ucf-101 reduces the level of ERS and apoptosis both in Vivo and in vitro.

In adult male mice (20-25 g), after a single dose, Ucf-101 reduces post ischemic myocardial apoptosis. And it also decreases myocardial infarct size in mice. In the PD rats, Ucf-101 improves the APO-induced rotational behavior. What’s more,  Ucf-101 reverses the reduction of DA neurons in vivo.
In conclusion, Ucf-101 is an anti-apoptotic agent that would specifically target caspase-independent cell death.


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[2]. Liu HR, et, al. Circulation. 2005 Jan 4;111(1):90-6.