Oxidized low-density lipoprotein suppresses mouse granulosa cell differentiation through disruption of the hypoxia-inducible factor 1 pathway

2017 ◽  
Vol 84 (12) ◽  
pp. 1306-1313
Author(s):  
Xiaoliang Chen ◽  
Yanhong Liu ◽  
Yanhong Shan ◽  
Xingyi Jin ◽  
Qingyang Shi ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Granulosa Cell ◽  
Low Density Lipoprotein ◽  
Hypoxia Inducible Factor ◽  
Density Lipoprotein ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Hypoxia Inducible Factor 1

Oxidized low-density lipoprotein (oxLDL) triggers hypoxia-inducible factor-1α (HIF-1α) accumulation via redox-dependent mechanisms

Blood ◽  
2003 ◽  
Vol 101 (12) ◽  
pp. 4847-4849 ◽  
Author(s):  
Vladimir A. Shatrov ◽  
Vadim V. Sumbayev ◽  
Jie Zhou ◽  
Bernhard Brüne
Keyword(s):  
Reporter Gene ◽  
Low Density Lipoprotein ◽  
Hypoxia Inducible Factor ◽  
Density Lipoprotein ◽  
Luciferase Reporter ◽  
Low Density ◽  
Mrna Levels ◽  
Oxidized Low Density Lipoprotein ◽  
Human Macrophages ◽  
Hypoxia Inducible Factor 1Α

Abstract Oxidized low-density lipoprotein (oxLDL) and macrophages play a central role in atherosclerosis. Here, we obtained evidence that oxLDL induced hypoxia-inducible factor-1α (HIF-1α) protein accumulation in human macrophages (Mono-Mac-6) under normoxia. HIF-1α accumulation was attenuated by pretreatment with the antioxidant N-acetyl-L-cysteine (NAC), the nitric oxide (NO) donor S-nitrosoglutathione (GSNO), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors such as diphenyleniodonium (DPI) or 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF), thus implicating the contribution of oxLDL-generated reactive oxygen species (ROS). Whereas oxLDL did not modulate HIF-1α mRNA levels, experiments with cycloheximide pointed to a translational mechanism in oxLDL action. HIF-1–dependent luciferase reporter gene analysis underscored HIF-1 transactivation. Our results indicate that oxLDL induced HIF-1α accumulation and HIF-1–dependent reporter gene activation in human macrophages via a redox-mediated pathway. This finding may suggest a role of HIF-1 in atherosclerosis and oxLDL-induced pathogenesis.

scholarly journals Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1-Mediated Autophagy in Human Granulosa Cells as an Alternative of Programmed Cell Death

Endocrinology ◽  
2006 ◽  
Vol 147 (8) ◽  
pp. 3851-3860 ◽  
Author(s):  
Nicole Duerrschmidt ◽  
Olga Zabirnyk ◽  
Marcin Nowicki ◽  
Albert Ricken ◽  
Fayez A. Hmeidan ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Dependent Manner ◽  
Oxidized Low Density Lipoprotein ◽  
Time Point

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 κ-carrageenan) abrogated the up-regulation of LOX-1. The oxLDL (100 μg/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.

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