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

Duerrschmidt, Nicole; Zabirnyk, Olga; Nowicki, Marcin; Ricken, Albert; Hmeidan, Fayez Abu; Blumenauer, Verona; Borlak, Jürgen; Spanel‐Borowski, Katharina

doi:10.1210/en.2006-0088

Cited by 95 publications

(80 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous in vitro studies have linked autophagy and apoptosis in granulosa cells to follicular atresia (57,58). Autophagosomes have been detected in granulosa cells of atretic follicles in several species including rat (59), ewe (60), bovine (61), characiform fish (62), goose (63), quail (64), and human (65). In addition, autophagic vacuoles were first reported in the regressing CL of humans and guinea pigs more than 40 y ago (66)(67)(68)(69).…”

Section: Discussionmentioning

confidence: 99%

Beclin-1 deficiency in the murine ovary results in the reduction of progesterone production to promote preterm labor

Gawriluk

Hong

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Autophagy is an important cellular process that serves as a companion pathway to the ubiquitin-proteasome system to degrade long-lived proteins and organelles to maintain cell homeostasis. Although initially characterized in yeast, autophagy is being realized as an important regulator of development and disease in mammals. Beclin1 (Becn1) is a putative tumor suppressor gene that has been shown to undergo a loss of heterozygosity in 40-75% of human breast, ovarian, and prostate cancers. Because Becn1 is a key regulator of autophagy, we sought to investigate its role in female reproduction by using a conditional knockout approach in mice. We find that pregnant females lacking Becn1 in the ovarian granulosa cell population have a defect in progesterone production and a subsequent preterm labor phenotype. Luteal cells in this model exhibit defective autophagy and a failure to accumulate lipid droplets needed for steroidogenesis. Collectively, we show that Becn1 provides essential functions in the ovary that are essential for mammalian reproduction.A utophagy is an evolutionarily conserved cellular process from yeast to mammals that recycles long-lived proteins and organelles to maintain cell energy homeostasis, and is classically activated through the nutrient sensor, mammalian target of rapamycin complex (1-3). Cellular material is encapsulated within a double phospholipid bilayer organelle called the "autophagosome," which fuses with a lysosome to degrade the internalized debris. Using genetic screens in yeast, more than 34 autophagyrelated (Atg) genes have been identified, with most having clear homologs in higher eukaryotes through protein-sequence identity (4-6). BECLIN1 (BECN1), a haploinsufficient tumor suppressor, is an essential autophagy protein that directs the initiation phase and maturation-fusion phase through its participation in two distinct phosphoinositide 3-kinase class III complexes (7-9). Autophagy is not only important for normal development, but it is linked to an array of diseases including neurodegenerative disorders, liver disease, heart disease, inflammatory diseases, and cancer (10, 11). We previously showed a role for BECN1 and autophagy in the establishment of the murine primordial follicle pools in a germ-line knockout model (12). In this study, we follow up on these results and investigate the role of BECN1 in ovarian granulosa cells.In mammals, the success of early pregnancy from embryo implantation to development of the conceptus depends on the function of an ephemeral endocrine gland, the "corpus luteum" (CL), which rapidly forms in the ovary from the remains of the ovulated follicle and migrating somatic cells through a process called "luteinization." Progesterone is an essential hormone that acts at several different levels during pregnancy, including the development of the endometrium for implantation of the embryo and the maintenance of pregnancy through quiescence of the myometrium (13,14). Luteal cells within the CL use cholesterol for steroidogenesis to produce progesterone ...

show abstract

Section: Discussionmentioning

confidence: 99%

Beclin-1 deficiency in the murine ovary results in the reduction of progesterone production to promote preterm labor

Gawriluk

Hong

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…The discovery of granulosa cell death via oxidised LDL (oxLDL)-dependent lectin-type oxLDL receptor (LOX1)-activated autophagy, however, suggests that autophagic forms of programmed cell death are also involved (Duerrschmidt et al 2006, Serke et al 2009). As obese women have increased levels of oxLDL (Mutlu-Türkoglu et al 2003), and consequently a higher incidence of autophagic granulosa cell death, this pathway could account for a higher rate of infertility in obese women (Duerrschmidt et al 2006). LOX1 stimulation by oxLDL has also been associated with an increased level of reactive oxygen species (ROS) leading to oxidative stress and apoptotic cell death.…”

Section: Ovaries and Testesmentioning

confidence: 99%

Autophagy in the endocrine glands

Weckman¹,

Ieva²,

Rotondo³

et al. 2014

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Autophagy is an important cellular process involving the degradation of intracellular components. Its regulation is complex and while there are many methods available, there is currently no single effective way of detecting and monitoring autophagy. It has several cellular functions that are conserved throughout the body, as well as a variety of different physiological roles depending on the context of its occurrence in the body. Autophagy is also involved in the pathology of a wide range of diseases. Within the endocrine system, autophagy has both its traditional conserved functions and specific functions. In the endocrine glands, autophagy plays a critical role in controlling intracellular hormone levels. In peptide-secreting cells of glands such as the pituitary gland, crinophagy, a specific form of autophagy, targets the secretory granules to control the levels of stored hormone. In steroid-secreting cells of glands such as the testes and adrenal gland, autophagy targets the steroid-producing organelles. The dysregulation of autophagy in the endocrine glands leads to several different endocrine diseases such as diabetes and infertility. This review aims to clarify the known roles of autophagy in the physiology of the endocrine system, as well as in various endocrine diseases.

show abstract

“…Another ROS source translates to a granulosa cell subtype without CK filaments, termed CK-negative (CK -) granulosa cell. It expresses the lectin-like oxidized low density lipoprotein receptor 1 (LOX-1), a specific scavenger receptor for oxLDL (Duerrschmidt et al, 2006;Serke et al, 2009). …”

Section: Danger In Preovulatory Follicles For Onset Of Inim Functionmentioning

confidence: 99%

Ovulation as danger signaling event of innate immunity

Spanel‐Borowski

2011

Molecular and Cellular Endocrinology

Self Cite

View full text Add to dashboard Cite

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

Cited by 95 publications

References 47 publications

Beclin-1 deficiency in the murine ovary results in the reduction of progesterone production to promote preterm labor

Beclin-1 deficiency in the murine ovary results in the reduction of progesterone production to promote preterm labor

Autophagy in the endocrine glands

Ovulation as danger signaling event of innate immunity

Contact Info

Product

Resources

About