Differential effects of 15-HPETE and 15-HETE on BHK-21 cell proliferation and macromolecular composition.
Arachidonate and/or linoleate metabolites have been implicated in modulating cell growth, replication and cell transformations. In studies with BHK-21 cells, we found lipoxygenase and cyclooxygenase inhibitors (NDGA and indomethacin, respectively) to be antiproliferative. Studies on the metabolism of arachidonic acid in BHK-21 cells have demonstrated that prostaglandin D2 is the major cyclooxygenase product, and 15-hydroxyeicosatetraenoic acid (15-HETE) is the major lipoxygenase product. Addition of D2 showed a significant decrease in the BHK-21 cell number showing antiproliferative action. Addition of lipoxygenase products, on the other hand, showed differential effects in that 15-HPETE decreased the cell number while 15-HETE increased. NDGA and 15-HPETE decreased DNA, RNA and protein contents, while 15-HETE significantly increased them. 5-HPETE and 5-HETE also showed similar results but were less potent than 15-H(P)ETEs. The differential effects of 15-HPETE and 15-HETE could be due to the generation of free radicals by the hydroperoxide and mitogenic response by hydroxide.
School of Life Sciences, University of Hyderabad, India.
Y V
YV
Kiran Kumar
A
A
Raghunathan
S
S
Sailesh
M
M
Prasad
M C
MC
Vemuri
P
P
Reddanna
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D006224:Cricetinae; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects*; D015289:Leukotrienes / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors; D046911:Macromolecular Substances; D009195:Peroxidase / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D008054:Lipid Peroxides; D016859:Lipoxygenase Inhibitors; D046911:Macromolecular Substances; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D009195:Peroxidase; D001094:Arachidonate 5-Lipoxygenase