Nitric oxide inhibits Oct-1 DNA binding activity in cultured vascular smooth muscle cells.

Abstract:

:Since Oct-1 is a ubiquitous DNA binding protein shown to play an important role in regulating cell proliferation and possess structural characteristics consistent with a nitric oxide (NO) target, we studied NO regulation of the DNA binding activity of Oct-1 in the A7R5 vascular smooth muscle cell (VSMC) line. Two NO donors, sodium nitroprusside (SNP) and S-nitroso-N-acetyl-penicillamine (SNAP) were directly added to the nuclear extract-oligonucleotide reaction mixture, respectively and the effect on Oct-1 DNA binding activity was evaluated by gel shift assay. Both NO donors (0.01-1 mM) inhibited the DNA binding activity of Oct-1. This inhibitory effect was not attenuated by dithiothreitol (DTT) (1 mM) while in contrast, DTT did antagonize the effect of diamide on Oct-1 DNA binding activity. The NO effect on Oct-1 has some specificity; as the NO donors had no effect on myc DNA binding activity. The inhibitory effect of NO donors was reproduced in A7R5 cells, without affecting their viability. These findings provide the first evidence that NO inhibits the DNA binding activity of Oct-1, probably through a cGMP independent mechanism and suggests that NO may inhibit mitogenesis in part through an effect on Oct-1 DNA binding activity in VSMCs.

journal_name

Life Sci

journal_title

Life sciences

authors

Liu XK,Abernethy DR,Andrawis NS

doi

10.1016/s0024-3205(97)01172-7

subject

Has Abstract

pub_date

1998-01-01 00:00:00

pages

739-49

issue

8

eissn

0024-3205

issn

1879-0631

pii

S0024320597011727

journal_volume

62

pub_type

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