Regulated expression of APE apurinic endonuclease mRNA during wound healing in porcine epidermis

被引:22
作者
Harrison, L
Galanopoulos, T
Ascione, AG
Antoniades, HN
Demple, B
机构
[1] HARVARD UNIV, SCH PUBL HLTH, DEPT MOLEC & CELLULAR TOXICOL, BOSTON, MA 02115 USA
[2] HARVARD UNIV, SCH MED, CTR BLOOD RES, BOSTON, MA 02115 USA
关键词
D O I
10.1093/carcin/17.2.377
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Abasic (AP) sites in DNA are cytotoxic and mutagenic and their repair is initiated by AP endonucleases. The major AP endonuclease of mammalian cells is encoded by the APE gene. Ape protein has also been proposed to modulate the activity of some transcription factors independently of its AP endonuclease activity. We investigated whether APE expression is coordinated with cell division, which could diminish mutagenesis. The level of APE mRNA was followed during wound healing in porcine epidermis, in which surgical wounding prompts rapid cell proliferation followed by a differentiation program to regenerate normal skin. In situ hybridization with a probe from human APE cDNA revealed strongly decreased expression in rapidly proliferating migrating cells during the first 1-3 days following wounding, succeeded by sharply increased APE expression that exceeded the pre-wounding levels by days 9-17. These changes were not observed in the surrounding undamaged tissue. In contrast to the foregoing in vivo results, APE expression in cultured primary human fibroblasts (IMR90) or myeloid leukemia cells (K562) was not coordinated with cell division. This biphasic APE expression during wound healing could relate to transcription factor regulation or it could allow unhindered DNA synthesis or prepare the developing epidermis to handle DNA damage. However, if transient under-expression of APE-encoded repair enzyme does occur, it might render regenerating skin especially vulnerable to mutagenesis during the cell proliferation phase.
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收藏
页码:377 / 381
页数:5
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