SMP30 deficiency in mice causes an accumulation of neutral lipids and phospholipids in the liver and shortens the life span
SMP30 deficiency in mice causes an accumulation of neutral lipids and phospholipids in the liver and shortens the life span
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DOI：
10.1016/j.bbrc.2004.01.091
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发表时间：
2004-03-12
影响因子：
3.1
通讯作者：
Maruyama, N
中科院分区：
文献类型：
--
作者：
Ishigami, A;Kondo, Y;Maruyama, N
衰老标志物蛋白-30(SMP30)是一种雄激素非依赖性因子，随着年龄的增长而减少。SMP30基因缺陷(SMP30Y/-)小鼠存活并能生育，但体重较轻，寿命比野生型短。在电子显微镜下，SMP30Y/-小鼠的肝细胞内有明显的脂滴，线粒体异常增大，线粒体脊模糊，溶酶体增大，充满电子致密小体。在SMP30Y/-小鼠的肝脏样本中，随着动物年龄的增长，中心静脉周围可见的脂滴的显著数量在大小和数量上显著增加。SMP30Y/-小鼠的中性脂肪、肝脏总甘油三酯和胆固醇的生化分析显示，它们的水平分别高出约3.6倍和3.3倍。而不是来自年龄匹配的野生型小鼠。此外，SMP30Y/-小鼠的肝脏总磷脂含量大约是野生型小鼠的3.7倍。通过薄层分析，SMP30Y/-小鼠肝脏脂类提取物中分别检测到磷脂酰乙醇胺、心磷脂、磷脂酰胆碱、磷脂酰丝氨酸和鞘磷脂的积累，这一结果有力地表明了SMP30缺乏对这些中性脂和磷脂代谢的深刻影响。可以想象，这种脂代谢的异常足以缩短SMP30缺陷小鼠的寿命。(C)2004 Elsevier Inc.保留所有权利。
Senescence marker protein-30 (SMP30) is an androgen-independent factor that decreases with aging. SMP30-deficient (SMP30Y/-) mice are viable and fertile but lower in body weight and shorter in life span than the wild-type. In the electron microscope, hepatocytes from SMP30Y/- but not the wild-type mice at 12 months of age clearly contained many lipid droplets, abnormally enlarged mitochondria with indistinct cristae, and enlarged lysosomes filled with electron-dense bodies. In liver specimens from SMP30Y/- mice, the marked number of lipid droplets visible around the central vein increased notably in size and amount as the animals aged. Biochemical analysis of neutral lipids, total hepatic triglyceride, and cholesterol from SMP30Y/- mice showed approximately 3.6- and 3.3-fold higher levels, respectively. than those from age-matched wild-type mice. Moreover, values for total hepatic phospholipids from SMP30Y/- mice were approximately 3.7-fold higher than those for their wild-type counterparts. By thin-layer chromatography analysis, phosphatidylethanolamine, cardiolipin, phosphatidylcholine, phosphatidylserine, and sphingomyelin accumulations were detected separately in lipid extracts from SMP30Y/- mouse livers and provided results that strongly indicate the profound effect of an SMP30 deficiency on the metabolism of these neutral lipids and phospholipids. Conceivably, this abnormality of lipid metabolism is sufficient to curtail the life span of SMP30-deficient mice. (C) 2004 Elsevier Inc. All rights reserved.