Nitric oxide inhibits polyamine-induced apoptosis in the human extravillous trophoblast cell line SGHPL-4.
BACKGROUND
Polyamines are regulators of proliferation and differentiation in mammalian cells. They are also known to regulate cell survival and apoptosis, although their precise function varies between cell types. We have investigated the effect of polyamines on the apoptosis of human extravillous trophoblasts.


METHODS
Using the extravillous trophoblast-derived cell line SGHPL-4 we performed time-lapse microscopy studies to evaluate the induction of apoptosis following exposure to polyamines.


RESULTS
The polyamines spermine, and to a lesser extent spermidine, were able to induce apoptosis in extravillous trophoblasts. The induction of apoptosis occurred rapidly and was accompanied by DNA fragmentation and morphological changes consistent with the onset of apoptosis. Apoptosis was inhibited by the broad-spectrum caspase inhibitor Z-VAD-fmk, although no activity was detected using assays for caspase-2, -3, -6, -8 or -9 activity. We demonstrated that an oxidation product of spermine accounted for the induction of apoptosis and implicated the formation of hydrogen peroxide as this oxidation product. We have also demonstrated that exposure to nitric oxide inhibited the onset of spermine-induced apoptosis.


CONCLUSIONS
Spermine and spermidine induce apoptosis in extravillous trophoblasts following their oxidation and the production of hydrogen peroxide. Nitric oxide is able to inhibit this apoptosis.
Dash
Philip R
PR
Department of Biochemistry and Immunology, St.George's Hospital Medical School, University of London, London SW17 ORE, UK.
Cartwright
Judith E
JE
Whitley
Guy St J
GS
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000737:chemistry / Q000378:metabolism; D002374:Catalase / Q000494:pharmacology; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006801:Humans; D009569:Nitric Oxide / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry / Q000378:metabolism; D011073:Polyamines / Q000494:pharmacology*; D011700:Putrescine / Q000494:pharmacology; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000378:metabolism / Q000494:pharmacology; D013997:Time Factors; D014327:Trophoblasts / Q000187:drug effects* / Q000502:physiology*
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D011073:Polyamines; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D013096:Spermine; D009569:Nitric Oxide; D002374:Catalase; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D013095:Spermidine; D011700:Putrescine