We have assessed the relative contribution of the thyroid hormones and noradrenaline (NA) on the calorigenic function of brown adipose tissue (BAT) as indicated by GDP binding and O2 consumption of BAT mitochondria. Male Wistar rats of 200 g body weight were made hypothyroid with 131I. Groups of animals were injected s.c., in divided doses, daily for 10 days, with thyroxine (2 micrograms/100 g body weight) or tri-iodothyronine (T3; 0.3 microgram/100 g body weight). Animals were used 7 days after bilateral or unilateral sympathetic nerve excision of BAT (Sx). Sham-operated rats were used as controls. In normal rats kept at 22 degrees C, GDP binding reached 94 +/- 24 pmol/mg protein; untreated hypothyroid rats had normal binding values whereas the T3-treated group showed an increased binding. Sx induced a sharp fall in the three groups (P < 0.01). After 24-h exposure to 4 degrees C GDP binding increased in normal rats to about 410% (P < 0.01) whereas binding failed to increase in response to cold in the untreated hypothyroid and the T3-treated groups. Sx reduced GDP binding in the three groups significantly (P < 0.01). The consumption of O2 by BAT mitochondria showed similar variations in response to Sx and to cold exposure as did GDP binding. The data indicated that, at room temperature, BAT calorigenesis can function without the thyroid hormones, though not without the catecholamines. The findings in rats exposed to cold showed that the lack of NA was significantly more effective than the lack of thyroid hormones in preventing the BAT hyperactive response. This does not negate an active role for T3 in BAT calorigenesis.
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http://dx.doi.org/10.1677/joe.0.1450579 | DOI Listing |
Nat Commun
January 2025
Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, QC, H3T 1J4, Canada.
Intense research on founding members of the RAS superfamily has defined our understanding of these critical signalling proteins, leading to the premise that small GTPases function as molecular switches dependent on differential nucleotide loading. The closest homologs of H/K/NRAS are the three-member RRAS family, and interest in the MRAS GTPase as a regulator of MAPK activity has recently intensified. We show here that MRAS does not function as a classical switch and is unable to exchange GDP-to-GTP in solution or when tethered to a lipid bilayer.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Warshel Institute for Computational Biology, School of Life and Health Sciences, School of Medicine, The Chinese University of Hong Kong (Shenzhen), Shenzhen 518172, China.
The parathyroid hormone type 1 receptor (PTH1R) plays a crucial role in modulating various physiological functions and is considered an effective therapeutic target for osteoporosis. However, a lack of detailed molecular and energetic information about PTH1R limits our comprehensive understanding of its activation process. In this study, we performed computational simulations to explore key events in the activation process, such as conformational changes in PTH1R, Gs protein coupling, and the release of guanosine diphosphate (GDP).
View Article and Find Full Text PDFRSC Adv
January 2025
University of Wuppertal, School of Mathematics and Natural Sciences Gaussstrasse 2042119 Wuppertal Germany
Betulinic acid and other herbal pentacyclic triterpenes have attracted interest in cancer research as these natural products induce apoptosis and suppress tumor progression. However, the molecular basis of the antitumor effect is still unknown. Here we show that monophthalates of betulinic acid and related triterpenes inhibit GDP/GTP exchange in oncogenic K-RAS4B proteins the PI3K/AKT downstream cascade.
View Article and Find Full Text PDFPlant Physiol
January 2025
Guizhou Engineering Research Center for Fruit Crops, Agricultural College, Guizhou University, Guiyang, Guizhou, China.
Light plays an important role in determining the L-ascorbate (AsA) pool size in plants, primarily through the transcriptional regulation of AsA metabolism-related genes. However, the specific mechanism of transcriptional induction responsible for light-dependent AsA biosynthesis remains unclear. In this study, we used a promoter sequence containing light-responsive motifs from GDP-L-galactose phosphorylase 2 (RrGGP2), a key gene involved in AsA overproduction in Rosa roxburghii fruits, to identify participating transcription factors.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Department of Pulmonary and Critical Care Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. Electronic address:
The small GTPase Ras is among the most frequently mutated genes and its mutations often drive oncogenesis across various cancers. While the role of NRas phosphorylation at S89 in the context of a Q61R mutation in melanoma genesis remains controversial, the impact of S89 phosphorylation on NRas function has not been fully elucidated. In this study, we employed the S89D phosphorylation-mimetic mutation and demonstrated that the S89D mutation alone activated all Ras isoforms by increasing the GTP-bound population, thereby promoting ERK phosphorylation and cell proliferation.
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