Application | Comment | Organism |
---|---|---|
medicine | blood platelet enzyme 12-LOX modulates FcgammaRIIa signaling and presents a viable therapeutic target in the prevention of immune-mediated thrombosis | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
ML355 | a selective 12-LOX inhibitor, blocks both FcgammaRIIa-induced platelet aggregation and (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate production | Homo sapiens | |
ML355 | a selective 12-LOX inhibitor, blocks both FcgammaRIIa-induced platelet aggregation and (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate production | Mus musculus |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
arachidonate + O2 | Mus musculus | - |
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate | - |
? | |
arachidonate + O2 | Homo sapiens | - |
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | O75342 | - |
- |
Mus musculus | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
blood platelet | high expression level of 12-LOX | Mus musculus | - |
blood platelet | high expression level of 12-LOX | Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
arachidonate + O2 | - |
Mus musculus | (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate | - |
? | |
arachidonate + O2 | - |
Homo sapiens | (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate | - |
? |
Synonyms | Comment | Organism |
---|---|---|
12(S)-lipoxygenase | - |
Mus musculus |
12(S)-lipoxygenase | - |
Homo sapiens |
12-LOX | - |
Mus musculus |
12-LOX | - |
Homo sapiens |
oxylipin-producing enzyme | - |
Mus musculus |
oxylipin-producing enzyme | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
malfunction | pharmacologic inhibition of 12-LOX in human platelets results in significant attenuation of FcgammaRIIa-mediated aggregation. Activation of the FcgammaRIIa receptor leads to immune-mediated thrombosis, which is often life threatening in patients undergoing heparin-induced thrombocytopenia or sepsis. Inhibiting FcgammaRIIa-mediated activation, e.g. by inhibiting the enzyme 12-LOX, in platelets limits thrombosis and is the principal target for prevention of immune-mediated platelet activation | Homo sapiens |
malfunction | platelets from transgenic mice expressing human FcgammaRIIa but deficient in platelet 12-LOX, fail to form normal platelet aggregates and exhibit deficiencies in Rap1 and aIIbbeta3 activation | Mus musculus |
additional information | platelets from transgenic mice expressing human FcgammaRIIa but deficient in platelet 12-LOX, fail to form normal platelet aggregates and exhibit deficiencies in Rap1 and aIIbbeta3 activation | Homo sapiens |
physiological function | murine platelets require 12-LOX for normal FcgammaRIIa-induced platelet aggregation | Mus musculus |
physiological function | platelet 12(S)-lipoxygenase (12-LOX), a highly expressed oxylipin-producing enzyme in the human platelet, is an essential component of FcgammaRIIa-mediated thrombosis. Platelet enzyme 12-LOX modulates FcgammaRIIa signaling and is essential for FcgammaRIIa-mediated platelet activation. 12-LOX is essential for FcgammaRIIa-induced phospholipase Cgamma2 activity leading to activation of calcium mobilization, Rap1 and protein kinase C activation, and subsequent activation of the integrin aIIbbeta3. 12-LOX regulates dense and a granule secretion in FcgammaRIIa-activated platelets | Homo sapiens |