Ensemble cryoEM elucidates the mechanism of insulin capture and degradation by human insulin degrading enzyme.

Insulin degrading enzyme (IDE) plays key roles in degrading peptides vital in type two diabetes, Alzheimer's, inflammation, and other human diseases. However, the process through which IDE recognizes peptides that tend to form amyloid fibrils remained unsolved. We used cryoEM to understand both the apo- and insulin-bound dimeric IDE states, revealing that IDE displays a large opening between the homologous ~55 kDa N- and C-terminal halves to allow selective substrate capture based on size and charge complementarity.

Induction of proteinases in the human preovulatory follicle of the menstrual cycle by human chorionic gonadotropin.

Objective: To explore the temporal expression in granulosa and theca cells of key members of the MMP and ADAMTS families across the periovulatory period in women to gain insight into their possible roles during ovulation and early luteinization.

Design: Experimental prospective clinical study and laboratory-based investigation.

Setting: University medical center and private IVF center.

Conformational states and recognition of amyloidogenic peptides of human insulin-degrading enzyme.

Insulin-degrading enzyme (IDE) selectively degrades the monomer of amyloidogenic peptides and contributes to clearance of amyloid β (Aβ). Thus, IDE retards the progression of Alzheimer's disease. IDE possesses an enclosed catalytic chamber that engulfs and degrades its peptide substrates; however, the molecular mechanism of IDE function, including substrate access to the chamber and recognition, remains elusive.

Activation of the PKC pathway stimulates ovarian cancer cell proliferation, migration, and expression of MMP7 and MMP10.

Postmenopausal women are at a higher risk of ovarian cancer due, in part, to increased levels of gonadotropins such as luteinizing hormone (LH). Gonadotropins and other stimuli are capable of activating two pathways, PKA and PKC, that are altered in ovarian cancer. To determine the role of LH on ovarian cancer, we explored the effects of human chorionic gonadotropin (hCG), an LH mimic, and an activator of the PKC pathway, phorbol-12-myristate 13-acetate (PMA), on ovarian cancer cell-cycle kinetics and apoptosis in Ovcar3 cells.

Up-regulation of oxytocin receptor expression at term is related to maternal body mass index.

Background: The likelihood of cesarean is in part related to maternal body mass index (BMI). Myometrial changes may be responsible.

Methods: Myometrial biopsies were collected from the upper edge of the hysterotomy from women undergoing scheduled cesarean with term, singleton gestations.

Ovarian expression and regulation of the stromelysins during the periovulatory period in the human and the rat.

The matrix metalloproteinases (MMPs) are postulated to facilitate follicular rupture. In the present study, expression of the stromelysins (MMP3, MMP10, MMP11) was analyzed in the periovulatory human and rat ovary. Human granulosa and theca cells were collected from the dominant follicle at various times after human chorionic gonadotropin (hCG).