Department of Biochemistry and Molecular Biology, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
FASEB J. 2012 Jan;26(1):169-80. doi: 10.1096/fj.11-184879. Epub 2011 Oct 3.
Long-chain polyunsaturated fatty acids (PUFAs) accumulate in mammalian testis during puberty and are essential for fertility. To investigate whether lysophospholipid acyltransferases determine the PUFA composition of testicular phospholipids during pubertal development, we compared their mRNA expression, in vitro activity, and specificity with the lipidomic profile of major phospholipids. The accumulation of PUFAs in phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine correlated with an induced lysophosphatidic acid acyltransferase (LPAAT)3 mRNA expression, increased microsomal LPAAT3 activity, and shift of LPAAT specificity to PUFA-coenzyme A. LPAAT3 was induced during germ cell maturation, as shown by immunofluorescence microscopy. Accordingly, differentiation of mouse GC-2spd(ts) spermatocytes into spermatides up-regulated LPAAT3 mRNA, increased the amount of polyunsaturated phospholipids, and shifted the specificity for the incorporation of deuterium-labeled docosahexaenoic acid toward phosphatidylcholine and phosphatidylethanolamine. Stable knockdown of LPAAT3 in GC-2spd(ts) cells significantly decreased microsomal LPAAT3 activity, reduced levels of polyunsaturated phosphatidylethanolamine species, and impaired cell proliferation/survival during geneticin selection. We conclude that the induction of LPAAT3 during germ cell development critically contributes to the accumulation of PUFAs in testicular phospholipids, thereby possibly affecting sperm cell production.
长链多不饱和脂肪酸（PUFAs）在青春期时在哺乳动物睾丸中积累，对生育能力至关重要。为了研究溶血磷脂酰基转移酶是否在青春期发育过程中决定睾丸磷脂的 PUFA 组成，我们将它们的 mRNA 表达、体外活性和特异性与主要磷脂的脂质组学图谱进行了比较。在磷脂酰胆碱、磷脂酰乙醇胺和磷脂酰丝氨酸中 PUFAs 的积累与诱导的溶血磷脂酸酰基转移酶（LPAAT）3 mRNA 表达、增加的微粒体 LPAAT3 活性以及 LPAAT 特异性向 PUFA-辅酶 A 的转变相关。LPAAT3 在生殖细胞成熟过程中被诱导，如免疫荧光显微镜所示。因此，小鼠 GC-2spd(ts) 精母细胞向精细胞的分化上调了 LPAAT3 mRNA，增加了多不饱和磷脂的含量，并改变了氘标记的二十二碳六烯酸掺入磷脂酰胆碱和磷脂酰乙醇胺的特异性。在 GC-2spd(ts) 细胞中稳定敲低 LPAAT3 显著降低了微粒体 LPAAT3 活性，降低了多不饱和磷脂酰乙醇胺种类的水平，并在遗传霉素选择过程中损害了细胞增殖/存活。我们得出结论，LPAAT3 在生殖细胞发育过程中的诱导对于睾丸磷脂中 PUFAs 的积累至关重要，从而可能影响精子细胞的产生。
