HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Maccarrone, M. Articles by Finazzi-Agrò, A. Search for Related Content PubMed PubMed Citation Articles by Maccarrone, M. Articles by Finazzi-Agrò, A.

(Journal of Leukocyte Biology. 2003;73:472-481.)
© 2003 by Society for Leukocyte Biology

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

Mauro Maccarrone^*, Natalia Battista, Mariantonia Meloni, Monica Bari, Grazia Galleri, Proto Pippia, Augusto Cogoli and Alessandro Finazzi-Agrò

^* Department of Biomedical Sciences, University of Teramo, Italy;
Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Italy;
Department of Physiological, Biochemical and Cellular Sciences, University of Sassari, Italy; and
Space Biology, ETH, Zürich, Switzerland

Correspondence: Mauro Maccarrone, Ph.D., Department of Biomedical Sciences, University of Teramo, Piazza A. Moro 45, 64100 Teramo, Italy. E-mail: Maccarrone{at}vet.unite.it

Creating conditions similar to those that occur during exposure of cells to microgravity induced a sixfold increase of apoptotic bodies and DNA fragments in human lymphocytes, paralleled by an early (within 2 h) fourfold increase in 5-lipoxygenase (5-LOX) activity and a fivefold decrease in mitochondrial membrane potential and increase in cytochrome c release (within 4 and 8 h, respectively). 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 65–70%. The intracellular calcium chelator EGTA-acetoxymethylester reduced 5-LOX activity and apoptosis to 30–40% 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 25–30% 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.

Key Words: arachidonate cascade • calcium • caspase • cyclooxygenase • mitochondrial membrane potential

This article has been cited by other articles:

				D. M. Simons, E. M. Gardner, and P. I. Lelkes Dynamic culture in a rotating-wall vessel bioreactor differentially inhibits murine T-lymphocyte activation by mitogenic stimuli upon return to static conditions in a time-dependent manner J Appl Physiol, April 1, 2006; 100(4): 1287 - 1292. [Abstract] [Full Text] [PDF]