Fujita T
Department of Molecular Pathology, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakaecho, Tokyo-, Itabashi-ku, 1730015, Japan.
Biochem Biophys Res Commun. 1999 Jan 8;254(1):1-4. doi: 10.1006/bbrc.1998.9841.
Senescence marker protein-30 (SMP30), which we previously identified, is notable for its androgen-independent decrease in the livers of aging rats. Hepatocytes and renal tubular epithelia express large amounts of SMP30 in their cytosol throughout the tissue-maturing process and adulthood, but its level decreases thereafter. Upon cloning cDNAs that encode SMP30 in rats, mice, and humans, we found that the amino acid sequence of SMP30 is well conserved with remarkable homology among these species. However, this gene, which is so strongly conserved in these higher animals, does not appear in yeast. We also determined the genome organization and 5' flanking region of SMP30 in mouse genome. In the meantime, SMP30 turned out be identical to a Ca2+-binding protein called regucalcin (RC). To learn how this protein functions, we transfected Hep G2 cells with human SMP30 cDNA so that these cells stably express large amounts of SMP30. The results suggest that SMP30 regulates Ca2+ homeostasis by enhancing Ca2+-pumping activity in the plasma membranes. Thus, SMP30 seems to play a critical role in the highly differentiated functions of the liver and kidney and to exert a major impact on Ca2+ homeostasis. If so, down-regulation of SMP30 with aging would attribute greatly to the related deterioration of these organs, as indicated in this brief overview of the structure, expression, and function of SMP30.
衰老标记蛋白-30（SMP30）是我们之前鉴定出的，其在衰老大鼠肝脏中的表达呈现雄激素非依赖性降低，这一点值得关注。在整个组织成熟过程及成年期，肝细胞和肾小管上皮细胞的胞质溶胶中都大量表达SMP30，但此后其水平会下降。在克隆大鼠、小鼠和人类中编码SMP30的cDNA后，我们发现SMP30的氨基酸序列在这些物种中具有高度保守性且同源性显著。然而，这个在高等动物中如此高度保守的基因在酵母中并未出现。我们还确定了小鼠基因组中SMP30的基因组结构和5'侧翼区域。与此同时，SMP30被证明与一种名为调节钙素（RC）的钙结合蛋白相同。为了解该蛋白的功能，我们用人类SMP30 cDNA转染Hep G2细胞，使这些细胞稳定大量表达SMP30。结果表明，SMP30通过增强质膜中的钙泵活性来调节钙稳态。因此，SMP30似乎在肝脏和肾脏的高度分化功能中发挥关键作用，并对钙稳态产生重大影响。如果是这样，随着衰老SMP30的下调将极大地归因于这些器官的相关功能衰退，正如对SMP30的结构、表达和功能的简要概述中所指出的那样。
