Retinoic acid-induced differentiation in a human neuroblastoma cell line is associated with an increase in nitric oxide synthesis.

Abstract:

:The human neuroblastoma cell line SK-N-BE, after incubation with 10 microM retinoic acid (RA) or 20 nM phorbol 12-myristate 13-acetate (PMA), underwent biochemical and morphological signs of differentiation within 10-14 days. In parallel, SK-N-BE cells produced significantly higher amounts of nitric oxide (NO) in comparison with controls, as assessed by the measurement of nitrite and nitrate in the culture supernatant and of NO synthase (NOS) activity in the cell lysates (measured as ability to convert [3H]arginine into [3H]citrulline and as NADPH diaphorase activity). Nitrite/nitrate production was abolished by adding the NO scavenger hemoglobin in the culture medium and was inhibited by aminoguanidine (AG, a selective inhibitor of the inducible NOS isoform) but not by the less selective inhibitor NG-nitro-L-arginine methylester (NAME). Western blotting experiments with monoclonal antibodies against the ncNOS and iNOS isoforms suggest that RA-elicited NOS activation is not attributable to an increased expression of the protein. NAME and AG were not able to revert inhibition of proliferation induced by RA, and the NO donor sodium nitroprusside did not mimic the effect of RA and PMA. These data indicate that increased NO synthesis does not mediate RA- or PMA-induced differentiation but may be an additional marker of differentiation into sympathetic-like neuronal cells.

journal_name

J Cell Physiol

authors

Ghigo D,Priotto C,Migliorino D,Geromin D,Franchino C,Todde R,Costamagna C,Pescarmona G,Bosia A

doi

10.1002/(SICI)1097-4652(199801)174:1<99::AID-JCP11

subject

Has Abstract

pub_date

1998-01-01 00:00:00

pages

99-106

issue

1

eissn

0021-9541

issn

1097-4652

pii

10.1002/(SICI)1097-4652(199801)174:1<99::AID-JCP11

journal_volume

174

pub_type

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