Duerrschmidt Nicole, Zabirnyk Olga, Nowicki Marcin, Ricken Albert, Hmeidan Fayez A, Blumenauer Verona, Borlak Jürgen, Spanel-Borowski Katharina
Institute of Anatomy, University of Leipzig, Liebigstrasse 13, D-04103 Leipzig, Germany.
Endocrinology. 2006 Aug;147(8):3851-60. doi: 10.1210/en.2006-0088. Epub 2006 May 11.
The LOX-1 receptor, identified on endothelial cells, mediates the uptake of oxidized low-density lipoprotein (oxLDL). The oxLDL-dependent LOX-1 activation causes endothelial cell apoptosis. We here investigated the presence of LOX-1 in granulosa cells from patients under in vitro fertilization therapy. We were interested in the oxLDL-dependent LOX-1 receptor biology, in particular in the induction of apoptosis. In the human ovary, LOX-1 was localized in regressing antral follicles. In granulosa cell cultures, oxLDL-induced mRNA expression of LOX-1 in a time- and dose-dependent manner. The LOX-1 inhibitors (anti-LOX-1 antibody and kappa-carrageenan) abrogated the up-regulation of LOX-1. The oxLDL (100 microg/ml) treatment caused the autophagy form of programmed cell death: 1) reorganization of the actin cytoskeleton at the 6-h time point; 2) uptake of YO-PRO, a marker for the early step of programmed cell death, before propidium iodide staining to signify necrosis; 3) absence of apoptotic bodies and cleaved caspase-3; 4) abundant vacuole formation at the ultrastructural level; and 5) decrease of the autophagosome marker protein MAP LC3-I at the 6-h time point indicative of autophagosome formation. We conclude that follicular atresia is not under the exclusive control of apoptosis. The LOX-1-dependent autophagy represents an alternate form of programmed cell death. Obese women with high blood levels of oxLDL may display an increased rate of autophagic granulosa cell death.
在内皮细胞上发现的凝集素样氧化低密度脂蛋白受体1（LOX-1）介导氧化低密度脂蛋白（oxLDL）的摄取。oxLDL依赖的LOX-1激活会导致内皮细胞凋亡。我们在此研究了体外受精治疗患者颗粒细胞中LOX-1的存在情况。我们关注oxLDL依赖的LOX-1受体生物学，特别是其对细胞凋亡的诱导作用。在人类卵巢中，LOX-1定位于退化的窦状卵泡。在颗粒细胞培养中，oxLDL以时间和剂量依赖的方式诱导LOX-1的mRNA表达。LOX-1抑制剂（抗LOX-1抗体和κ-卡拉胶）消除了LOX-1的上调。oxLDL（100微克/毫升）处理导致程序性细胞死亡的自噬形式：1）在6小时时间点肌动蛋白细胞骨架重组；2）在碘化丙啶染色表明坏死之前，摄取YO-PRO，这是程序性细胞死亡早期阶段的标志物；3）不存在凋亡小体和裂解的半胱天冬酶-3；4）在超微结构水平有大量液泡形成；5）在6小时时间点自噬体标志物蛋白微管相关蛋白轻链3-I（MAP LC3-I）减少，表明自噬体形成。我们得出结论，卵泡闭锁并非仅受细胞凋亡的控制。LOX-1依赖的自噬代表程序性细胞死亡的另一种形式。血液中oxLDL水平高的肥胖女性可能表现出自噬性颗粒细胞死亡速率增加。
