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.

scholarly journals The neurorepellent, Slit2, prevents macrophage lipid loading by inhibiting CD36-dependent binding and internalization of oxidized low-density lipoprotein

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bushra Yusuf ◽  
Ilya Mukovozov ◽  
Sajedabanu Patel ◽  
Yi-Wei Huang ◽  
Guang Ying Liu ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Super Resolution ◽  
Low Density ◽  
Dependent Manner ◽  
Oxidized Low Density Lipoprotein ◽  
Cortical Actin ◽  
Cytoskeletal Remodeling ◽  
Atherosclerotic Lesions ◽  
Modified Lipoproteins

AbstractAtherosclerosis is characterized by retention of modified lipoproteins, especially oxidized low density lipoprotein (oxLDL) within the sub-endothelial space of affected blood vessels. Recruited monocyte-derived and tissue-resident macrophages subsequently ingest oxLDL by binding and internalizing oxLDL via scavenger receptors, particularly CD36. The secreted neurorepellent, Slit2, acting through its transmembrane receptor, Roundabout-1 (Robo-1), was previously shown to inhibit recruitment of monocytes into nascent atherosclerotic lesions. The effects of Slit2 on oxLDL uptake by macrophages have not been explored. We report here that Slit2 inhibits uptake of oxLDL by human and murine macrophages, and the resulting formation of foam cells, in a Rac1-dependent and CD36-dependent manner. Exposure of macrophages to Slit2 prevented binding of oxLDL to the surface of cells. Using super-resolution microscopy, we observed that exposure of macrophages to Slit2 induced profound cytoskeletal remodeling with formation of a thick ring of cortical actin within which clusters of CD36 could not aggregate, thereby attenuating binding of oxLDL to the surface of cells. By inhibiting recruitment of monocytes into early atherosclerotic lesions, and the subsequent binding and internalization of oxLDL by macrophages, Slit2 could represent a potent new tool to combat individual steps that collectively result in progression of atherosclerosis.

Prolactin, LH, and estradiol-17β in utilization of lipoprotein substrate by porcine granulosa cells in vitro

1988 ◽  
Vol 66 (5) ◽  
pp. 561-566 ◽  
Author(s):  
K. Rajkumar ◽  
P. Klingshorn ◽  
P. J. Chedrese ◽  
B. D. Murphy
Keyword(s):  
Granulosa Cell ◽  
Cell Cultures ◽  
Granulosa Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Porcine Granulosa Cells ◽  
Progesterone Synthesis ◽  
Serum Free Conditions

Porcine granulosa cells cultured under serum free conditions responded by increased progesterone secretion to the addition of the leuteotropic hormones, LH, prolactin, and estradiol. Provision of extracellular substrate for steroidogenesis in the form of porcine high density lipoprotein or low density lipoprotein enhanced progesterone accumulation by granulosa cell cultures. Estradiol, LH, and prolactin all greatly increased progesterone accumulation in the presence of either high or low density lipoproteins. Increases in progesterone accumulation following addition of prolactin or LH in combination with estradiol suggested the presence of a synergistic interaction among leuteotropins. Pre-exposure of granulosa cell cultures to estradiol increased the subsequent stimulatory effect of prolactin on lipoprotein utilization. It is concluded that all three leuteotropins function to enhance and may interact in the utilization of extracellular lipoprotein substrate for progesterone synthesis.

scholarly journals Oxidized Low Density Lipoprotein Induced Caspase-1 Mediated Pyroptotic Cell Death in Macrophages: Implication in Lesion Instability?

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e62148 ◽  
Author(s):  
Jing Lin ◽  
Xiling Shou ◽  
Xiaobo Mao ◽  
Jiangchuan Dong ◽  
Nilesh Mohabeer ◽  
...  
Keyword(s):  
Cell Death ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Caspase 1

Autophagy and Apoptosis in the Response of Human Vascular Endothelial Cells to Oxidized Low-Density Lipoprotein

Cardiology ◽  
2015 ◽  
Vol 132 (1) ◽  
pp. 27-33 ◽  
Author(s):  
Yanlin Zhang ◽  
Ying Xie ◽  
Shoujiang You ◽  
Qiao Han ◽  
Yongjun Cao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
P53 Protein ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Positive Staining ◽  
Low Density ◽  
Dependent Manner ◽  
Oxidized Low Density Lipoprotein ◽  
Concentration Dependent Manner

Objectives: Oxidized low-density lipoprotein (ox-LDL) may induce autophagy, apoptosis, necrosis or proliferation of cultured endothelial cells depending on the concentration and exposure time. Our previous studies found that ox-LDL exposure for 6 h increases the autophagic level of human umbilical vein endothelial cells (HUVECs) in a concentration-dependent manner. The present study investigates the relationship between autophagy and apoptosis in HUVECs exposed to ox-LDL. Methods: Flow cytometry and Western blot were used to study the apoptotic and autophagic phenomena. The contribution of autophagic and apoptotic mechanisms to ox-LDL-induced upregulation of MAP1-LC3, beclin1 and p53 protein levels were assessed by pretreatment with the autophagic inhibitors 3-MA and Atg5 small interfering (si)RNA, as well as z-vad-fmk, an apoptosis inhibitor. Results: ox-LDL induced the apoptosis of HUVECs in a concentration-dependent way. The increased expression of the autophagic proteins, LC3-II and beclin1, can be reversed by 3-MA and z-vad-fmk pretreatment. 3-MA and Atg5 siRNA increased the ox-LDL-induced increases of the p53 protein level and the annexin V-positive staining, which was decreased by z-vad-fmk. Conclusion: These results suggest that overstimulation of ox-LDL can induce autophagy and apoptosis in HUVECs. Inhibition of apoptosis leads to an inhibition of autophagy induced by ox-LDL. However, inhibition of autophagy leads to an increase in the ox-LDL-induced apoptosis.

scholarly journals LOX-1 scavenger receptor mediates calcium-dependent recognition of phosphatidylserine and apoptotic cells

2005 ◽  
Vol 393 (1) ◽  
pp. 107-115 ◽  
Author(s):  
Jane E. Murphy ◽  
Daryl Tacon ◽  
Philip R. Tedbury ◽  
Jonathan M. Hadden ◽  
Stuart Knowling ◽  
...  
Keyword(s):  
Cultured Cells ◽  
Low Density Lipoprotein ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
Dependent Manner ◽  
Oxidized Low Density Lipoprotein ◽  
Bivalent Cation ◽  
Calcium Dependent

The LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1) scavenger receptor regulates vascular responses to oxidized-low-density-lipoprotein particles implicated in atherosclerotic plaque formation. LOX-1 is closely related to C-type lectins, but the mechanism of ligand recognition is not known. Here we show that human LOX-1 recognizes a key cellular phospholipid, PS (phosphatidylserine), in a Ca2+-dependent manner, both in vitro and in cultured cells. A recombinant, folded and glycosylated LOX-1 molecule binds PS, but not other phospholipids. LOX-1 recognition of PS was maximal in the presence of millimolar Ca2+ levels. Mg2+ was unable to substitute for Ca2+ in LOX-1 binding to PS, indicating a Ca2+-specific requirement for bivalent cations. LOX-1-mediated recognition of PS-containing apoptotic bodies was dependent on Ca2+ and was decreased to background levels by bivalent-cation chelation, LOX-1-blocking antibodies or PS-containing liposomes. The LOX-1 membrane protein is thus a Ca2+-dependent phospholipid receptor, revealing novel recognition of phospholipids by mammalian lectins.

scholarly journals Chlamydia pneumoniae Augments the Oxidized Low-Density Lipoprotein-Induced Death of Mouse Macrophages by a Caspase-Independent Pathway

2005 ◽  
Vol 73 (7) ◽  
pp. 4315-4322 ◽  
Author(s):  
Kambiz Yaraei ◽  
Lee Ann Campbell ◽  
Xiaodong Zhu ◽  
W. Conrad Liles ◽  
Cho-chou Kuo ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cell Death ◽  
Chlamydia Pneumoniae ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Mouse Macrophages ◽  
The Impact

ABSTRACT Chlamydia pneumoniae is a common respiratory pathogen that is associated with an increased risk of cardiovascular disease. However, the mechanisms by which C. pneumoniae contributes to cardiovascular disease have not been determined yet. C. pneumoniae infection may accelerate the death of cells within atherosclerotic lesions and contribute to the formation of unstable lesions. To test this hypothesis, the impact of C. pneumoniae infection on the death of lipid-loaded mouse macrophages was investigated. It was observed that RAW 264.7 cells are highly susceptible to the toxic effects of oxidized low-density lipoprotein (LDL) and exhibit markers of cell death within 24 h of treatment with as little as 5 μg/ml oxidized LDL. Subsequent infection with either live C. pneumoniae or heat-killed or UV-inactivated C. pneumoniae at a low multiplicity of infection for 24 to 72 h stimulated both additional binding of annexin V and the uptake of propidium iodide. Thus, C. pneumoniae augments the effects of oxidized LDL on cell death independent of a sustained infection. However, unlike oxidized LDL, C. pneumoniae infection does not activate caspase 3 or induce formation of the mitochondrial transition pore or the fragmentation of DNA, all of which are classical markers of apoptosis. Furthermore, primary bone marrow macrophages isolated from mice deficient in Toll-like receptor 2 (TLR-2) but not TLR-4 are resistant to C. pneumoniae-induced death. These data suggest that C. pneumoniae kills cells by a caspase-independent pathway and that the process is potentially mediated by activation of TLR-2.

Phenolic antioxidants attenuate neuronal cell death following uptake of oxidized low-density lipoprotein

2000 ◽  
Vol 29 (12) ◽  
pp. 1222-1233 ◽  
Author(s):  
Hagen Schroeter ◽  
Robert J Williams ◽  
Rubeta Matin ◽  
Leslie Iversen ◽  
Catherine A Rice-Evans
Keyword(s):  
Cell Death ◽  
Low Density Lipoprotein ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Density Lipoprotein ◽  
Phenolic Antioxidants ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein
Sign in / Sign up

Export Citation Format

Share Document