Browsing by Author "Sancho, Teresa"
Now showing 1 - 2 of 2
Results Per Page
Sort Options
- Effect of maternal restricted diet during late gestation on muscle and bone development in sheep offspringPublication . Estêvão, Dulce; Harrison, Adrian; McKenzie, S. H.; Ribeiro, Luís Pedro; Tygesen, M. P.; Sancho, Teresa; Power, DeborahChanges in intrauterine environment, including nutrient availability, have been associated with fetal programming, contributing to different phenotypes which may determine health and susceptibility to disease throughout life. These changes seem to be mediated through alterations in both anabolic and catabolic hormone levels of maternal, placental and/or fetal origin. The present work aimed to evaluate how maternal under-nutrition during late pregnancy affects muscle and bone growth. Pregnant ewes were divided into two groups, one fed ad libitum and the other fed a restricted diet (50% of total energy requirements) during the last 6 weeks of gestation. Three twin carrying ewes from each feeding group were euthanized 6 days pre parturition. The remaining ewes gave birth normally and reared their lambs. At approximately day 30 post partum, 5 lambs from each of the feeding groups were euthanized and samples collected. Nutrient restriction during late gestation did not affect intrauterine axial growth, although weight at birth and the muscle weight were significantly lower than the ad libitum fed lamb fetuses. Bone development is less affected cf muscle development during periods of maternal feed restriction; however, catch-up growth of muscle occurs when lambs (30 days post-parturition) have access to adequate rations. In utero irrespective of maternal nutrient supply dry muscle mass is correlated (r=0.94) to bone development (bone weight, femur length and femur mineral density). In contrast, post partum growth of and skeleton are less tightly coupled and unaffected by the events in utero. A detailed examination of how maternal nutrient supply affects endocrine parameters in utero will be required to assess if it affects susceptibility post-partum to endocrine dysfunction.
- Stress-induced protein disaggregation in the endoplasmic reticulum catalysed by BiPPublication . Melo, Eduardo; Konno, Tasuku; Farace, Ilaria; Awadelkareem, Mosab Ali; Skov, Lise R.; Teodoro, Fernando; Sancho, Teresa; Paton, Adrienne W.; Paton, James C.; Fares, Matthew; Paulo, Pedro M. R.; Zhang, Xin; Avezov, EdwardProtein synthesis is supported by cellular machineries that ensure polypeptides fold to their native conformation, whilst eliminating misfolded, aggregation prone species. Protein aggregation underlies pathologies including neurodegeneration. Aggregates' formation is antagonised by molecular chaperones, with cytoplasmic machinery resolving insoluble protein aggregates. However, it is unknown whether an analogous disaggregation system exists in the Endoplasmic Reticulum (ER) where -30% of the proteome is synthesised. Here we show that the ER of a variety of mammalian cell types, including neurons, is endowed with the capability to resolve protein aggregates under stress. Utilising a purpose-developed protein aggregation probing system with a sub-organellar resolution, we observe steady-state aggregate accumulation in the ER. Pharmacological induction of ER stress does not augment aggregates, but rather stimulate their clearance within hours. We show that this dis-sagregation activity is catalysed by the stress-responsive ER molecular chaperone - BiP. This work reveals a hitherto unknow, non-redundant strand of the proteostasis-restorative ER stress response.