Alcain F J, Löw H, Crane F L
Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
Biochem Biophys Res Commun. 1994 Aug 30;203(1):16-21. doi: 10.1006/bbrc.1994.2142.
Treatment of CCl 39 cells with the impermeable iron II chelator bathophenanthroline disulfonate (BPS) inhibits both DNA synthesis and transplasma membrane electron transport. The inhibition persists when the BPS is removed, and the extract from 10(6) cells contains up to 1.28 nmoles iron II chelated to BPS. The BPS iron II chelate itself is not inhibitory. Both DNA synthesis and electron transport are restored by addition of microM iron II or iron III compounds to extracted cells. Other impermeable chelators for iron II give similar inhibition, whereas the iron III-specific Tiron or copper-specific bathocuproine sulfonate do not inhibit. The inhibition differs from the permeable iron III chelator inhibition of ribonucleotide reductase, because inhibition of DNA synthesis by the permeable chelators is reversed when chelator is removed. The response to growth factors also differs, with no impermeable chelator inhibition on 10% fetal calf serum contrasting to inhibition by permeable chelators. DNA synthesis with both activation of tyrosine kinase with EGF plus insulin or by thrombin or ceruloplasmin led to protein kinase C activation as inhibited by the impermeable chelators. It is proposed that an iron available on the cell surface is required for DNA synthesis and plasma membrane electron transport.
用不可渗透的铁II螯合剂4,7-二苯基-1,10-菲咯啉二磺酸（BPS）处理CCl 39细胞，可抑制DNA合成和跨质膜电子传递。去除BPS后抑制作用仍然存在，10⁶个细胞的提取物中含有多达1.28纳摩尔与BPS螯合的铁II。BPS铁II螯合物本身并无抑制作用。向提取的细胞中添加微摩尔浓度的铁II或铁III化合物可恢复DNA合成和电子传递。其他不可渗透的铁II螯合剂也有类似的抑制作用，而铁III特异性的钛铁试剂或铜特异性的磺酸铜试剂则无抑制作用。这种抑制作用不同于可渗透的铁III螯合剂对核糖核苷酸还原酶的抑制作用，因为去除螯合剂后，可渗透螯合剂对DNA合成的抑制作用会逆转。对生长因子的反应也有所不同，10%胎牛血清对DNA合成无不可渗透螯合剂抑制作用，这与可渗透螯合剂的抑制作用形成对比。用表皮生长因子（EGF）加胰岛素激活酪氨酸激酶、或用凝血酶或铜蓝蛋白激活酪氨酸激酶所引发的DNA合成，均会导致蛋白激酶C激活，而这会受到不可渗透螯合剂的抑制。有人提出，DNA合成和质膜电子传递需要细胞表面可利用的铁。
