Granulosa Cell Subtypes Vary in Response to Oxidized Low-Density Lipoprotein as Regards Specific Lipoprotein Receptors and Antioxidant Enzyme Activity

作者：Serke H; Bausenwein J; Hirrlinger J; Nowicki M; Vilser C; Jogschies P; Hmeidan F A; Blumenauer V; Spanel Borowski K^*

来源：Journal of Clinical Endocrinology & Metabolism, 2010, 95(7): 3480-3490.

DOI：10.1210/jc.2009-2654

Context: The oxidized low-density lipoprotein (oxLDL) and its lectin-like oxLDL receptor-1 (LOX-1) are found in the follicular fluid and in granulosa cells. Lipoprotein receptors and antioxidant enzymes could differ in granulosa cell subtypes.
Objective: Our aim was to reveal cell-specific responses under oxLDL treatment.
Design and Setting: We conducted basic research at the Institute of Anatomy and the Clinic of Reproductive Medicine.
Patients: Women undergoing in vitro fertilization therapy participated in the study.
Main Outcome Measures: Cultures of cytokeratin-positive/negative (CK(+)/CK(-)) granulosa cells and of cumulus cells were treated with 150 mu g/ml oxLDL or native LDL under serum-free conditions for up to 36 h. Dead cells were determined by uptake of propidium iodide. LOX-1, toll-like receptor 4, and cluster of differentiation 36 (CD36) were examined in lysates by Western blots. The enzyme activities were determined in lysates and in supernatants.
Results: Under oxLDL treatment, predominantly CK(+) cells underwent nonapoptotic cell death. Receptors showed a cell-specific pattern of up-regulation: toll-like receptor 4 in CK(+) cells, LOX-1 in CK(-) cells, and CD36 in cumulus cells. An antioxidant ranking occurred: superoxide dismutase activity in CK(+) cells, total glutathione in CK(-) cells, and catalase activity in cumulus cells. The supernatants of oxLDL-treated CK(+) cell cultures contained more catalase activity than in controls, whereas a moderate increase was noted for glutathione peroxidase (GPx) in supernatants of CK(-) and cumulus cells.
Conclusions: Catalase/GPx activity in the supernatants may be due to cell death or to secretion. Oxidative stress could be sensed by CK(+) cells and indicated by changes in catalase/GPx activity in the follicular fluid during ovarian disorders. (J Clin Endocrinol Metab 95: 3480-3490, 2010)

• 出版日期2010-7