Platelet-type 12-LOX

The acetylene compounds - Panaxynol and falcarindiol, isolated from the roots of Saposhnikovia divaricata (Turcz.) Schischk. (Umbelliferae), selectively inhibited 5-LOX (ICso = 2 pM), leukocyte-type 12-LOX (IC50 = 1 pM), platelet-type 12-LOX (IC50 = 67 pM), and 15-LOX (IC50 = 4 pM). The same compounds had only marginal effects on COX activities with IC50 > 100 pM [126]. Bidens campylotheca Schultz Bip. ssp. campylotheca (Compositae) is a Hawaiian folk medicine for throat, stomach and asthmatic disorders. The polyacetylenes isolated from the aerial parts of the plants, such... 

Hinokitiol is a tropolone type natural compound isolated from the wood of Chymacyparis taiwanesis. The compound has been utilized as a natural antimicrobial agent in hair tonics, toothpastes, cosmetics and food supplements. Hinokitiol was evaluated on five different arachidonic acid metabolic pathways for the mechanism of action of anti-inflammatory effects. It has been found to be a potent inhibitor with IC50 values of 0.1 pM against platelet-type 12-LOX and 50 pM against leukocyte-type 12-LOX. It also inhibited soybean 5-LOX enzyme (IC50 = 17 pM). However, hinokitiol had almost no effects on COX-1 and COX-2 enzymes. Similar inhibition profiles were also observed on synthetic tropolone derivatives [168]. 

One possible integrator of these 12(S)-HETE signaling mechanisms in tumor cells is the pleiotropic transcription factor NE-kB, which plays an important role in the control of cell proliferation and apoptosis. Using PC-3 prostate cancer cells, we have shown that either overexpression of the platelet-type 12-LOX or exogenously added 12(S)-HETE activates NF-kB (Kandouz et al.,... 

AG is oxygenated to 12-HPETE glycerol ester by porcine leukocyte 12-LOX and in COS-7 cells transfected with leukocyte 12-LOX, but not by platelet-type 12-LOX (Moody et al., 2001). It is not metabolized by potato or human 5-LOX (Kozak, Gupta, et al., 2002). 2-AG is metabolized by 15-LOX, the rates indicating that it is preferred to arachidonic add as a substrate. 15(5)-HPETE glycerol ester is formed via 15-LOX metabohsm of 2-AG in human epidermal keratinocy tes (Kozak, Gupta, et al., 2002). 

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