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Similar membrane potential and cytochrome c release were observed in isolated mitochondria treated with physiological amounts of 5-LOX and were enhanced by creating conditions similar to those that occur during exposure of cells to microgravity. 5-LOX inhibitors, 5,8,11,14-eicosatetraynoic acid and caffeic acid, completely prevented apoptosis, whereas the phospholipase A2 inhibitor methyl-arachidonoyl fluorophosphonate and the 5-LOX activating protein inhibitor MK886 reduced it to 65\u201370%. The intracellular calcium chelator EGTA-acetoxymethylester reduced 5-LOX activity and apoptosis to 30\u201340% of controls, whereas the p38 mitogen-activated protein kinase inhibitor SB203580 was ineffective. The caspase-3 and caspase-9 inhibitors Z-Asp(OCH3)-Glu(OCH3)-Val-Asp(OCH3)-fluoromethylketone (FMK) and Z-Leu-Glu(OCH3)-His-Asp(OCH3)-FMK reduced apoptotic bodies to 25\u201330% of the control cells. Finally, creating conditions similar to those that occur during exposure of cells to microgravity did not induce apoptosis in human lymphoma U937 cells, which did not express an active 5-LOX.<\/jats:p>","DOI":"10.1189\/jlb.0602295","type":"journal-article","created":{"date-parts":[[2003,3,26]],"date-time":"2003-03-26T17:44:27Z","timestamp":1048700667000},"page":"472-481","source":"Crossref","is-referenced-by-count":64,"title":["Creating conditions similar to those that occur during exposure of cells to microgravity induces apoptosis in human lymphocytes by 5-lipoxygenase-mediated mitochondrial uncoupling and cytochrome c release"],"prefix":"10.1093","volume":"73","author":[{"given":"Mauro","family":"Maccarrone","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, University of Teramo , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Battista","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariantonia","family":"Meloni","sequence":"additional","affiliation":[{"name":"Department of Physiological, Biochemical and Cellular Sciences, University of Sassari , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Bari","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia","family":"Galleri","sequence":"additional","affiliation":[{"name":"Department of Physiological, Biochemical and Cellular Sciences, University of Sassari , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Proto","family":"Pippia","sequence":"additional","affiliation":[{"name":"Department of Physiological, Biochemical and Cellular Sciences, University of Sassari , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto","family":"Cogoli","sequence":"additional","affiliation":[{"name":"Space Biology, ETH , Z\u00fcrich , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Finazzi-Agr\u00f2","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2003,4,1]]},"reference":[{"key":"2023033019045864600_jlb0472-cit-B1","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/7331","article-title":"Gene expression in space","volume":"5","author":"Hammond","year":"1999","journal-title":"Nat. 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