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51.
Lisa Eifler Annett Hoffmann Isabel Viola Wagner Nora Klöting Lena Sahlin Thomas Ebert Beate Jessnitzer Ulrike Lössner Michael Stumvoll Olle Söder Mathias Fasshauer Susan Kralisch 《生物化学与生物物理学报:疾病的分子基础》2018,1864(10):3292-3297
Objectives
Female reproductive dysfunction occurs in patients with pathological loss of adipose tissue, i.e. lipodystrophy (LD). However, mechanisms remain largely unclear and treatment effects of adipocyte-derived leptin have not been assessed in LD animals.Methods
In the current study, C57Bl/6 LD mice on a low-density lipoprotein receptor knockout background were treated with leptin or saline for 8?weeks and compared to non-LD controls.Results
The number of pups born was 37% lower in breeding pairs consisting of LD female mice x non-LD male mice (n?=?3.3) compared to LD male mice x non-LD female mice (n?=?5.2) (p?<?0.05). Mean uterus weight was significantly lower in the saline-treated LD group (18.8?mg) compared to non-LD controls (52.9?mg; p?<?0.0001) and increased significantly upon leptin treatment (46.5?mg; p?<?0.001). The mean number of corpora lutea per ovary was significantly lower in saline-treated LD animals compared to non-LD controls (p?<?0.01) and was restored to non-LD control levels by leptin (p?<?0.05). Mechanistically, mRNA expression of ovarian follicle-stimulating hormone receptor (p?<?0.01) and estrogen receptor β (p?<?0.05), as well as of pituitary luteinizing hormone β subunit (p?<?0.001) and follicle-stimulating hormone β subunit (p?<?0.05), was significantly upregulated in LD mice compared to non-LD controls. In addition, mean time to vaginal opening as a marker of puberty onset was delayed by 12.5?days in LD mice (50.9?days) compared to non-LD controls (38.4?days; p?<?0.001).Conclusions
Female LD animals show impaired fertility which is restored by leptin. Future studies should assess leptin as a subfertility treatment in human leptin-deficiency disorders. 相似文献52.
A Larsson M Karlsson M Sahlin B M Sj?berg 《The Journal of biological chemistry》1988,263(33):17780-17784
The small subunit of ribonucleoside-diphosphate reductase (EC 1.17.4.1) is a homodimer. Its catalytic site contains one tyrosyl radical, which is localized to Tyr-122 in one of its polypeptide chains. The engineered Tyr-122----Phe protein was used to demonstrate that it is possible to form a correct ferric iron center in vitro in the absence of Tyr-122. Heterodimers, consisting of one Tyr-122-containing polypeptide chain and one Phe-122-containing polypeptide chain, were constructed. The heterodimer population contained one-half the amount of tyrosyl radical as compared to a homodimer with Tyr-122, i.e. every second heterodimer contains a tyrosyl radical. Thus, one Tyr-122 is sufficient for radical formation. Radical-containing heterodimers are catalytically competent. 相似文献
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Although bacteria are unicellular organisms, they have the ability to act in concert by synthesizing and detecting small diffusing autoinducer molecules. The phenomenon, known as quorum sensing, has mainly been proposed to serve as a means for cell-density measurement. Here, we use a cell-based model of growing bacterial microcolonies to investigate a quorum-sensing mechanism at a single cell level. We show that the model indeed predicts a density-dependent behavior, highly dependent on local cell-clustering and the geometry of the space where the colony is evolving. We analyze the molecular network with two positive feedback loops to find the multistability regions and show how the quorum-sensing mechanism depends on different model parameters. Specifically, we show that the switching capability of the network leads to more constraints on parameters in a natural environment where the bacteria themselves produce autoinducer than compared to situations where autoinducer is introduced externally. The cell-based model also allows us to investigate mixed populations, where non-producing cheater cells are shown to have a fitness advantage, but still cannot completely outcompete producer cells. Simulations, therefore, are able to predict the relative fitness of cheater cells from experiments and can also display and account for the paradoxical phenomenon seen in experiments; even though the cheater cells have a fitness advantage in each of the investigated groups, the overall effect is an increase in the fraction of producer cells. The cell-based type of model presented here together with high-resolution experiments will play an integral role in a more explicit and precise comparison of models and experiments, addressing quorum sensing at a cellular resolution. 相似文献
56.
Muscle ammonia metabolism during isometric contraction in humans 总被引:1,自引:0,他引:1
57.
Cell proliferation affects both cellular geometry and topology in a growing tissue, and hence rules for cell division are key to understanding multicellular development. Epithelial cell layers have for long times been used to investigate how cell proliferation leads to tissue-scale properties, including organism-independent distributions of cell areas and number of neighbors. We use a cell-based two-dimensional tissue growth model including mechanics to investigate how different cell division rules result in different statistical properties of the cells at the tissue level. We focus on isotropic growth and division rules suggested for plant cells, and compare the models with data from the Arabidopsis shoot. We find that several division rules can lead to the correct distribution of number of neighbors, as seen in recent studies. In addition we find that when also geometrical properties are taken into account other constraints on the cell division rules result. We find that division rules acting in favor of equally sized and symmetrically shaped daughter cells can best describe the statistical tissue properties. 相似文献
58.
Torrents E Westman M Sahlin M Sjöberg BM 《The Journal of biological chemistry》2006,281(35):25287-25296
The opportunistic pathogen Pseudomonas aeruginosa, which causes serious nosocomial infections, is a gamma-proteobacterium that can live in many different environments. Interestingly P. aeruginosa encodes three ribonucleotide reductases (RNRs) that all differ from other well known RNRs. The RNR enzymes are central for de novo synthesis of deoxyribonucleotides and essential to all living cells. The RNR of this study (class Ia) is a complex of the NrdA protein harboring the active site and the allosteric sites and the NrdB protein harboring a tyrosyl radical necessary to initiate catalysis. P. aeruginosa NrdA contains an atypical duplication of the N-terminal ATP-cone, an allosteric domain that can bind either ATP or dATP and regulates the overall enzyme activity. Here we characterized the wild type NrdA and two truncated NrdA variants with precise N-terminal deletions. The N-terminal ATP-cone (ATP-c1) is allosterically functional, whereas the internal ATP-cone lacks allosteric activity. The P. aeruginosa NrdB is also atypical with an unusually short lived tyrosyl radical, which is efficiently regenerated in presence of oxygen as the iron ions remain tightly bound to the protein. The P. aeruginosa wild type NrdA and NrdB proteins form an extraordinarily tight complex with a suggested alpha4beta4 composition. An alpha2beta2 composition is suggested for the complex of truncated NrdA (lacking ATP-c1) and wild type NrdB. Duplication or triplication of the ATP-cone is found in some other bacterial class Ia RNRs. We suggest that protein modularity built on the common catalytic core of all RNRs plays an important role in class diversification within the RNR family. 相似文献
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60.
Mansour Akbari Karin Solvang-Garten Audun Hanssen-Bauer Nora Valeska Lieske Henrik Sahlin Pettersen Grete Klippenvåg Pettersen David M. Wilson Hans E. Krokan Marit Otterlei 《DNA Repair》2010,9(7):785-795
Uracil-DNA glycosylase, UNG2, interacts with PCNA and initiates post-replicative base excision repair (BER) of uracil in DNA. The DNA repair protein XRCC1 also co-localizes and physically interacts with PCNA. However, little is known about whether UNG2 and XRCC1 directly interact and participate in a same complex for repair of uracil in replication foci. Here, we examine localization pattern of these proteins in live and fixed cells and show that UNG2 and XRCC1 are likely in a common complex in replication foci. Using pull-down experiments we demonstrate that UNG2 directly interacts with the nuclear localization signal-region (NLS) of XRCC1. Western blot and functional analysis of immunoprecipitates from whole cell extracts prepared from S-phase enriched cells demonstrate the presence of XRCC1 complexes that contain UNG2 in addition to separate XRCC1 and UNG2 associated complexes with distinct repair features. XRCC1 complexes performed complete repair of uracil with higher efficacy than UNG2 complexes. Based on these results, we propose a model for a functional role of XRCC1 in replication associated BER of uracil. 相似文献