scholarly journals Occludin protects secretory cells from ER stress by facilitating SNARE-dependent apical protein exocytosis

2020 ◽  
Vol 117 (9) ◽  
pp. 4758-4769 ◽  
Author(s):  
Tao Zhou ◽  
Yunzhe Lu ◽  
Chongshen Xu ◽  
Rui Wang ◽  
Liye Zhang ◽  
...  
Keyword(s):  
Er Stress ◽  
Protein Secretion ◽  
Milk Proteins ◽  
Late Pregnancy ◽  
Mutant Mice ◽  
Snare Proteins ◽  
Secretory Cells ◽  
Tissue Polarity ◽  
Pregnancy And Lactation ◽  
Dependent Protein

Tight junctions (TJs) are fundamental features of both epithelium and endothelium and are indispensable for vertebrate organ formation and homeostasis. However, mice lackingOccludin(Ocln) develop relatively normally to term. Here we show thatOclnis essential for mammary gland physiology, as mutant mice fail to produce milk. Surprisingly,Oclnnull mammary glands showed intact TJ function and normal epithelial morphogenesis, cell differentiation, and tissue polarity, suggesting thatOclnis not required for these processes. Using single-cell transcriptomics, we identified milk-producing cells (MPCs) and found they were progressively more prone to endoplasmic reticulum (ER) stress as protein production increased exponentially during late pregnancy and lactation. Importantly,Oclnloss in MPCs resulted in greatly heightened ER stress; this in turn led to increased apoptosis and acute shutdown of protein expression, ultimately leading to lactation failure in the mutant mice. We show that the increased ER stress was caused by a secretory failure of milk proteins inOclnnull cells. Consistent with an essential role in protein secretion, Occludin was seen to reside on secretory vesicles and to be bound to SNARE proteins. Taken together, our results demonstrate thatOclnprotects MPCs from ER stress by facilitating SNARE-dependent protein secretion and raise the possibility that other TJ components may participate in functions similar toOcln.

scholarly journals Interaction of late pregnancy and lactation in rats

Reproduction ◽  
1999 ◽  
Vol 115 (2) ◽  
pp. 341-347 ◽  
Author(s):  
T. R. Koiter ◽  
H. Moes ◽  
N. Valkhof ◽  
S. Wijkstra
Keyword(s):  
Late Pregnancy ◽  
Pregnancy And Lactation

ANALYSIS OF RIBOSOMES AND POLYSOMES DERIVED FROM RABBIT MAMMARY GLANDS DURING PREGNANCY AND LACTATION

1971 ◽  
Vol 49 (4) ◽  
pp. 667-NP ◽  
Author(s):  
I. D. HERRIMAN ◽  
G. D. BAIRD ◽  
JUDY M. BRUCE
Keyword(s):  
Electron Microscopy ◽  
Density Gradient ◽  
Gradient Analysis ◽  
Late Pregnancy ◽  
Sucrose Density Gradient ◽  
Mammary Glands ◽  
Pregnancy And Lactation

SUMMARY Whole-ribosome and polysome-enriched fractions were prepared from the mammary glands of rabbits during late pregnancy and lactation. The composition of the fractions was determined by sucrose density gradient analysis and electron microscopy. The range of size of polysomal aggregates was similar in the late-pregnant and lactating gland, with aggregates containing five to nine ribosomal units predominating. However, the amount of polysomes relative to monosomes was invariably found to increase after parturition. The greater portion of this increase was accounted for by the increased abundance of aggregates containing five to nine units.

Influence of temperature on maternity roost selection by noctule bats (Nyctalus noctula) and Leisler’s bats (N. leisleri) in Białowieża Primeval Forest, Poland

2006 ◽  
Vol 84 (6) ◽  
pp. 900-907 ◽  
Author(s):  
Ireneusz Ruczyński
Keyword(s):  
Late Pregnancy ◽  
Ground Level ◽  
Data Logger ◽  
Primeval Forest ◽  
Tree Cavities ◽  
Roost Selection ◽  
Pregnancy And Lactation ◽  
Maximum Temperatures ◽  
Białowieża Primeval Forest ◽  
Nyctalus Noctula

This study tests whether the temperature of tree cavities determines their selection by bats in Białowieża Primeval Forest (BPF), eastern Poland. Using a data logger, I simultaneously measured the temperature in cavities selected by bats as roosts and the temperature in available but unselected cavities. The maternity roosts chosen by noctule bats, Nyctalus noctula (Schreber, 1774), and Leisler’s bats, N. leisleri (Kuhl, 1817), during late pregnancy and lactation were warmer than unoccupied cavities, but temperature ranges in the two types of cavity did not differ. A logistic regression model showed that the mean cavity temperature during the night (2200–0400) and the minimum cavity temperature over a 24 h period were crucial for roost selection. This suggests that female noctule and Leisler’s bats selected roosts that promoted juvenile growth and used tree cavities that could save them energy while they were active because the cavity temperatures were close to the lower critical temperature of their thermoneutral zone. I also suggest that selection of warmer cavities minimized the bats' energy expenditure prior to emergence from the roost and that passive rewarming inside the cavity was an important factor in minimizing energetic costs of roosting by bats in BPF. Mean and maximum temperatures recorded near tree trunks increased with the height at which the temperature was measured (ground level, 10, 20, and 30 m), suggesting that bats can gain thermal benefits from insolation of the trunk by selecting highly placed cavities, as was observed in BPF.

Abstract 3665: COL4A1 and COL4A2 Mutations cause Genetically Modifiable Cerebrovascular Diseases

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Marion Jeanne ◽  
Yi-Chinn Weng ◽  
Michelle de Leau ◽  
Cassandre Labelle-Dumais ◽  
Berkeley W Kauffman ◽  
...  
Keyword(s):  
Er Stress ◽  
Cell Biology ◽  
Phenotypic Variability ◽  
Cerebrovascular Diseases ◽  
Basement Membranes ◽  
Mutant Mice ◽  
Genetic Modifiers ◽  
Cellular Mechanisms ◽  
Cerebral Magnetic Resonance Imaging ◽  
Genetic Context

Mutations in the type IV collagen alpha 1 gene (COL4A1) cause Cerebrovascular Diseases (CVDs) in mice and human patients. Patients with COL4A1 mutations suffer from a broad range of CVDs, from infantile porencephaly to debilitating or fatal intracerebral hemorrhage (ICH), to subclinical cerebral microbleeds, suggesting that environmental and other genetic factors may influence their phenotypes. COL4A1 is one of the most abundant proteins in basement membranes and forms heterotrimers with COL4A2. Among possible pathogenic mechanisms are cellular stress due to the toxic intracellular aggregation of the COL4A1 and COL4A2 proteins and/or their absence in the basement membrane. Our first goal is to identify the relative contributions of COL4A1 and COL4A2 mutations to sporadic ICH and to understand the cellular mechanisms and genetic complexity underlying the disease. We identified novel COL4A1 mutations and for the first time, we discovered COL4A2 mutations in a cohort of 96 patients with sporadic ICH. Using a cell-based assay we determined that the mutations impair COL4A1 and COL4A2 secretion. We showed that mutant COL4A1 or COL4A2 proteins accumulate within the cell where they titrate normal COL4A1 and COL4A2 proteins. Interestingly, we found that some of the mutations can ultimately result in endoplasmic reticulum (ER) stress and activation of the Unfolded Protein Response. Our second goal was to test the hypothesis that differences in genetic context could contribute to phenotypic variability in human patients. Thus, we characterized CVD in Col4a1 mutant mice with two different genetic backgrounds. Using cerebral magnetic resonance imaging and histological analysis, we show that one or more genetic modifiers from the CAST/EiJ strain significantly reduce the size and frequency of ICHs detected in Col4a1 mutant mice on a C57BL/6J background. In conclusion, we found that both COL4A1 and COL4A2 mutations cause ICH in human patients, our results support that ER stress could be involved in the pathogenesis and we showed that genetic context is crucial for expressivity and severity of the CVD. We predict that ongoing experiments to better understand the cell biology of COL4A1 and COL4A2 mutations and the mechanisms of genetic modification could lead to targeted therapeutics to reduce the risk of CVD in patients with COL4A1 or COL4A2 mutations.

scholarly journals Pregnancy- and lactation-associated osteoporosis with vertebral fractures: a systematic review

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ying Qian ◽  
Lei Wang ◽  
Lili Yu ◽  
Weimin Huang
Keyword(s):  
Back Pain ◽  
Vertebral Fractures ◽  
Data Extraction ◽  
Treatment Options ◽  
Osteoporotic Fractures ◽  
Late Pregnancy ◽  
Mean Value ◽  
Thoracolumbar Region ◽  
Pregnancy And Lactation ◽  
Z Scores

Abstract Background To review, analyze and characterize the pregnancy and lactation-related osteoporosis (PLO) with vertebral fractures based on the extraction data in the previous studies. Methods A comprehensive literature search of electronic databases including the PubMed, Embase and Web of Science was conducted from January 1st,1990 to December 1st, 2020. The enrolled data were pooled to analyze the baseline characteristics, clinical features, risk factors and treatment options. Results A total of 65 articles with 338 cases were enrolled for data extraction. The enrolled cases aged from 19 to 47 years, with a mean value of 35.7 years old. The average body mass index (BMI) was 22.2 kg/m2 ranged from 16.0 to 39.0 kg/m2. Of the 173 cases, 149 cases with vertebral fractures occurred in the first pregnancy, 19 cases in the second pregnancy, four cases in the third pregnancy and one case in the fourth pregnancy. Up to 91.5% of the back pain occurred within the last 3 months of pregnancy and the first 3 months after delivery. The most involved vertebral levels were L2, L1 and T12 accounting for 32.6% of all the fractures. The average fracture numbers were 4.4 levels per patient. The lumbar Z-scores were mostly recorded with a mean value of − 3.2 ranged from − 7.8 to 0. Conclusions PLO with vertebral fractures is a rare clinical entity, which is more likely to occur in older and thinner pregnant women. Back pain is the clinical complaint and mostly occurs in the late pregnancy and early lactation periods. Most vertebral fractures appear in the first pregnancy but it can occur in any time of pregnancy. Thoracolumbar region is the mostly involved region. As compared with postmenopausal osteoporotic fractures, PLO usually has multiple levels fractures. Bisphosphonates are the most widely used treatment so far, however, many factors need to be taken into account to decide which drug to choose in PLO and further studies are necessary for clear recommendation in the future.

scholarly journals Expression of a hypomorphic Pomc allele alters leptin dynamics during late pregnancy

2020 ◽  
Vol 245 (1) ◽  
pp. 115-127 ◽  
Author(s):  
Hui Yu ◽  
Zoe Thompson ◽  
Sylee Kiran ◽  
Graham L Jones ◽  
Lakshmi Mundada ◽  
...  
Keyword(s):  
Fat Mass ◽  
Energy Homeostasis ◽  
Leptin Receptor ◽  
Late Pregnancy ◽  
Placental Development ◽  
Hypomorphic Mutation ◽  
Protein Levels ◽  
Maximal Arc ◽  
Hypothalamic Arcuate Nucleus ◽  
Pregnancy And Lactation

Proopiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus (ARC) are essential for normal energy homeostasis. Maximal ARC Pomc transcription is dependent on neuronal Pomc enhancer 1 (nPE1), located 12 kb upstream from the promoter. Selective deletion of nPE1 in mice decreases ARC Pomc expression by 70%, sufficient to induce mild obesity. Because nPE1 is located exclusively in the genomes of placental mammals, we questioned whether its hypomorphic mutation would also alter placental Pomc expression and the metabolic adaptations associated with pregnancy and lactation. We assessed placental development, pup growth, circulating leptin and expression of Pomc, Agrp and alternatively spliced leptin receptor (LepR) isoforms in the ARC and placenta of Pomc∆1/∆1 and Pomc+/+ dams. Despite indistinguishable body weights, lean mass, food intake, placental histology and Pomc expression and overall pregnancy outcomes between the genotypes, Pomc ∆1/∆1 females had increased pre-pregnancy fat mass that paradoxically decreased to control levels by parturition. However, Pomc∆1/∆1 dams had exaggerated increases in circulating leptin, up to twice of that of the typically elevated levels in Pomc+/+ mice at the end of pregnancy, despite their equivalent fat mass. Pomc∆1/∆1dams also had increased placental expression of soluble leptin receptor (LepRe), although the protein levels of LEPRE in circulation were the same as Pomc+/+ controls. Together, these data suggest that the hypomorphic Pomc∆1/∆1 allele is responsible for the perinatal super hyperleptinemia of Pomc∆1/∆1 dams, possibly due to upregulated leptin secretion from individual adipocytes.

scholarly journals SLY1 and Syntaxin 18 specify a distinct pathway for procollagen VII export from the endoplasmic reticulum

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Cristina Nogueira ◽  
Patrik Erlmann ◽  
Julien Villeneuve ◽  
António JM Santos ◽  
Emma Martínez-Alonso ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Fusion ◽  
Protein Secretion ◽  
Family Members ◽  
Retrograde Transport ◽  
Cytoplasmic Domain ◽  
Snare Complex ◽  
Snare Proteins ◽  
General Protein

TANGO1 binds and exports Procollagen VII from the endoplasmic reticulum (ER). In this study, we report a connection between the cytoplasmic domain of TANGO1 and SLY1, a protein that is required for membrane fusion. Knockdown of SLY1 by siRNA arrested Procollagen VII in the ER without affecting the recruitment of COPII components, general protein secretion, and retrograde transport of the KDEL-containing protein BIP, and ERGIC53. SLY1 is known to interact with the ER-specific SNARE proteins Syntaxin 17 and 18, however only Syntaxin 18 was required for Procollagen VII export. Neither SLY1 nor Syntaxin 18 was required for the export of the equally bulky Procollagen I from the ER. Altogether, these findings reveal the sorting of bulky collagen family members by TANGO1 at the ER and highlight the existence of different export pathways for secretory cargoes one of which is mediated by the specific SNARE complex containing SLY1 and Syntaxin 18.

scholarly journals Ligilactobacillus salivarius PS2 Supplementation during Pregnancy and Lactation Prevents Mastitis: A Randomised Controlled Trial

2021 ◽  
Vol 9 (9) ◽  
pp. 1933
Author(s):  
Esther Jiménez ◽  
Susana Manzano ◽  
Dietmar Schlembach ◽  
Krzysztof Arciszewski ◽  
Rocio Martin ◽  
...  
Keyword(s):  
Placebo Group ◽  
Post Partum ◽  
Controlled Trial ◽  
Late Pregnancy ◽  
Probiotic Strain ◽  
Study Groups ◽  
Rank Test ◽  
Double Blind ◽  
Pregnancy And Lactation ◽  
Randomised Controlled

Mastitis is considered one of the main reasons for unwanted breastfeeding cessation. This study aimed to investigate the preventive effect of the probiotic strain Ligilactobacillus salivarius PS2 on the occurrence of mastitis in lactating women. In this multicountry, multicenter, randomized, double-blind, placebo-controlled trial, 328 women were assigned to the probiotic or the placebo group. The intervention started from the 35th week of pregnancy until week 12 post-partum. The primary outcome was the incidence (hazard) rate of mastitis, defined as the presence of at least two of the following symptoms: breast pain, breast erythema, breast engorgement not relieved by breastfeeding, and temperature > 38 °C. The probability of being free of mastitis during the study was higher in the probiotic than in the placebo group (p = 0.022, Kaplan–Meier log rank test) with 9 mastitis cases (6%) vs. 20 mastitis cases (14%), respectively. The hazard ratio of the incidence of mastitis between both study groups was 0.41 (0.190–0.915; p = 0.029), indicating that women in the probiotic group were 58% less likely to experience mastitis. In conclusion, supplementation of L. salivarius PS2 during late pregnancy and early lactation was safe and effective in preventing mastitis, which is one of the main barriers for continuing breastfeeding.

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