Hormones as Effective Regulators of Short SERPINA1 Transcripts Encoding Alpha1-antitrypsin Bioactive Peptides in VitroстатьяКраткое сообщениеТезисы
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Дата последнего поиска статьи во внешних источниках: 1 февраля 2021 г.
Аннотация:Alpha1-antitrypsin (AAT) is the most abundant SERine Proteinase INhibitor (serpin) in human plasma. C-terminal domain of the protein encoded by SERPINA1 gene exon 5 is the precursor of biologically active peptides, which have been found in humans in pathological states [Cercek L & Cercek B, 1992; Chang WC et al., 2008; Zhou J et al., 2010; Dichtl et al., 2000; Blaurock N. et al., 2016] as well as in normal condition (nNIF - neonatal NET-inhibitory factor) [Yost, 2016]. Previously we identified endogenous short SERPINA1 transcripts in hepatocellular carcinoma cell line HepG2. These transcripts may potentially contribute to the production of the active peptides along with the established proteolytic pathway. Here we show that in HepG2 cells steroid hormones and prolactin affect short transcripts expression, while the impact on the synthesis of the long transcripts is much less prominent. Prolactin, 17β-estradiol, and cortisol appear to be the down-regulators with maximum 4-, 2,2- and 4,4-fold inhibitory activity, respectively, at 10(-8)M. In contrast, testosterone and progesterone upregulate the expression of the short transcripts with maximum 3,2- and 3-fold elevation at 10(-7)M and 10(-6)M, respectively. Because hepatocellular carcinoma is more common in men than in women and considering that peptides act in favor of the tumor, our results may partially explain such a disparity in sex predisposition. Moreover, our results suggest that mother’s hormones, such as progesterone, may potentially drive nNIF production and may explain why NET-inhibitory peptides level rapidly decreases in the circulation of the infant shortly after delivery [Yost, 2016].