迈向哺乳动物衰老的生物标志物：碳酸酐酶III

Towards a biomarker of mammalian senescence: carbonic anhydrase III.

作者信息

Wohlrab H, Bronson R T, Lu R C, Nemeth V

机构信息

Department of Cell Physiology, Boston Biomedical Research Institute, MA 02114.

出版信息

Biochem Biophys Res Commun. 1988 Aug 15;154(3):1130-6. doi: 10.1016/0006-291x(88)90258-6.

DOI:10.1016/0006-291x(88)90258-6

PMID:3136767

Abstract

Three proteins (D2, D3, D4) have been identified in the male Fischer 344 rat liver that decrease their concentration dramatically to virtually zero during the transition from physiological maturity to senescence. D3 (Mr 28 kDa), absent (or at a very low concentration) from the livers of newborns and females of all ages, reaches at 60 days (sexual maturity) its maximum concentration, which declines almost linearly thereafter. A homologous protein (CNBr peptide map) occurs in the BALB/c mouse under similar conditions. D3 was purified and since its N-terminal is blocked, digested with CNBr. SDS-PAGE-separated peptides were blotted upon Immobilon and sequenced. The partial sequence matches that of rat carbonic anhydrase III. Treatment of senescent rats with 5 alpha-dihydrotestosterone restores D4 completely, yet D2 and D3 only partially, towards their maximum life-time concentration. Thus senescence-related factors (e.g. hepatic androgen receptor) aside from serum testosterone are responsible for the disappearance of the three proteins from the senescent liver.

摘要

在雄性Fischer 344大鼠肝脏中已鉴定出三种蛋白质（D2、D3、D4），在从生理成熟到衰老的转变过程中，它们的浓度急剧下降至几乎为零。D3（分子量28 kDa）在新生大鼠和所有年龄段雌性大鼠的肝脏中不存在（或浓度极低），在60天（性成熟）时达到其最大浓度，此后几乎呈线性下降。在类似条件下，BALB/c小鼠中存在一种同源蛋白质（CNBr肽图）。D3被纯化，由于其N端被封闭，用CNBr进行消化。将SDS-PAGE分离的肽转移到Immobilon上并进行测序。部分序列与大鼠碳酸酐酶III的序列匹配。用5α-二氢睾酮处理衰老大鼠，可使D4完全恢复，而D2和D3仅部分恢复至其最大寿命浓度。因此，除血清睾酮外，衰老相关因素（如肝脏雄激素受体）是导致衰老肝脏中这三种蛋白质消失的原因。