Mitochondrial membrane transitions in heart and other organs of a hibernator

1988 ◽  
Vol 254 (3) ◽  
pp. E378-E383
Author(s):  
J. K. Raison ◽  
M. L. Augee ◽  
R. C. Aloia
Keyword(s):  
Body Temperature ◽  
Membrane Lipids ◽  
Accurate Determination ◽  
Thermal Response ◽  
Heart Tissue ◽  
Early Summer ◽  
Brown Fat ◽  
Critical Temperatures ◽  
Spermophilus Lateralis ◽  
And Function

Critical temperatures (T) for transitions in both lipid structure and enzyme function of mitochondrial membranes from liver, kidney, brown fat, and heart tissues were determined for the hibernator Spermophilus lateralis at two weekly intervals from early summer to late autumn and during hibernation. For all tissues T fell into one of three groups: those below 4 degrees C (the minimal level of accurate determination), those centered about a mean of 11.9 +/- 1.4 degrees C, and those centered about a mean of 20.9 +/- 1.8 degrees C. The T for tissues from torpid animals and from heart, at all sampling periods, was below 4 degrees C. For liver, kidney, and brown fat the mean T was approximately 21 degrees C in early summer but was lowered later in the season in a two-step process, falling to below 4 degrees C before the animals were exposed to cold and entering torpor. It is concluded that for mitochondria the thermal response of the membrane lipids is altered such that the transition in structure and function is always below the minimum body temperature likely to be experienced by this animal. Heart tissue is exceptional in that the transition is at a temperature consistent with a body temperature of torpor even in summer-active animals.

scholarly journals Using field observations to inform thermal hydrology models of permafrost dynamics with ATS (v0.83)

2015 ◽  
Vol 8 (4) ◽  
pp. 3235-3292 ◽  
Author(s):  
A. L. Atchley ◽  
S. L. Painter ◽  
D. R. Harp ◽  
E. T. Coon ◽  
C. J. Wilson ◽  
...  
Keyword(s):  
Carbon Sink ◽  
Thermal Response ◽  
Field Measurements ◽  
Early Summer ◽  
Active Layer Thickness ◽  
Earth System ◽  
Model Refinement ◽  
System Models ◽  
Developed Surface ◽  
Earth System Models

Abstract. Climate change is profoundly transforming the carbon-rich Arctic tundra landscape, potentially moving it from a carbon sink to a carbon source by increasing the thickness of soil that thaws on a seasonal basis. However, the modeling capability and precise parameterizations of the physical characteristics needed to estimate projected active layer thickness (ALT) are limited in Earth System Models (ESMs). In particular, discrepancies in spatial scale between field measurements and Earth System Models challenge validation and parameterization of hydrothermal models. A recently developed surface/subsurface model for permafrost thermal hydrology, the Advanced Terrestrial Simulator (ATS), is used in combination with field measurements to calibrate and identify fine scale controls of ALT in ice wedge polygon tundra in Barrow, Alaska. An iterative model refinement procedure that cycles between borehole temperature and snow cover measurements and simulations functions to evaluate and parameterize different model processes necessary to simulate freeze/thaw processes and ALT formation. After model refinement and calibration, reasonable matches between simulated and measured soil temperatures are obtained, with the largest errors occurring during early summer above ice wedges (e.g. troughs). The results suggest that properly constructed and calibrated one-dimensional thermal hydrology models have the potential to provide reasonable representation of the subsurface thermal response and can be used to infer model input parameters and process representations. The models for soil thermal conductivity and snow distribution were found to be the most sensitive process representations. However, information on lateral flow and snowpack evolution might be needed to constrain model representations of surface hydrology and snow depth.

scholarly journals Impact of Membrane Lipids on UapA and AzgA Transporter Subcellular Localization and Activity in Aspergillus nidulans

2021 ◽  
Vol 7 (7) ◽  
pp. 514
Author(s):  
Mariangela Dionysopoulou ◽  
George Diallinas
Keyword(s):  
Plasma Membrane ◽  
Subcellular Localization ◽  
Aspergillus Nidulans ◽  
Membrane Lipids ◽  
Membrane Lipid ◽  
Lipid Biosynthesis ◽  
Transport Kinetics ◽  
Negative Effect ◽  
And Function

Recent biochemical and biophysical evidence have established that membrane lipids, namely phospholipids, sphingolipids and sterols, are critical for the function of eukaryotic plasma membrane transporters. Here, we study the effect of selected membrane lipid biosynthesis mutations and of the ergosterol-related antifungal itraconazole on the subcellular localization, stability and transport kinetics of two well-studied purine transporters, UapA and AzgA, in Aspergillus nidulans. We show that genetic reduction in biosynthesis of ergosterol, sphingolipids or phosphoinositides arrest A. nidulans growth after germling formation, but solely blocks in early steps of ergosterol (Erg11) or sphingolipid (BasA) synthesis have a negative effect on plasma membrane (PM) localization and stability of transporters before growth arrest. Surprisingly, the fraction of UapA or AzgA that reaches the PM in lipid biosynthesis mutants is shown to conserve normal apparent transport kinetics. We further show that turnover of UapA, which is the transporter mostly sensitive to membrane lipid content modification, occurs during its trafficking and by enhanced endocytosis, and is partly dependent on autophagy and Hect-type HulARsp5 ubiquitination. Our results point out that the role of specific membrane lipids on transporter biogenesis and function in vivo is complex, combinatorial and transporter-dependent.

scholarly journals The fate and function of glycosphingolipid glucosylceramide

2003 ◽  
Vol 358 (1433) ◽  
pp. 869-873 ◽  
Author(s):  
Gerrit van Meer ◽  
Jasja Wolthoorn ◽  
Sophie Degroote
Keyword(s):  
Cellular Differentiation ◽  
Membrane Lipids ◽  
Early Stage ◽  
Cellular Level ◽  
Mature Stage ◽  
Storage Diseases ◽  
Head Groups ◽  
Biological Studies ◽  
Intracellular Membrane Transport ◽  
And Function

In higher eukaryotes, glucosylceramide is the simplest member and precursor of a fascinating class of membrane lipids, the glycosphingolipids. These lipids display an astounding variation in their carbohydrate head groups, suggesting that glycosphingolipids serve specialized functions in recognition processes. It is now realized that they are organized in signalling domains on the cell surface. They are of vital importance as, in their absence, embryonal development is inhibited at an early stage. Remarkably, individual cells can live without glycolipids, perhaps because their survival does not depend on glycosphingolipid–mediated signalling mechanisms. Still, these cells suffer from defects in intracellular membrane transport. Various membrane proteins do not reach their intracellular destination, and, indeed, some intracellular organelles do not properly differentiate to their mature stage. The fact that glycosphingolipids are required for cellular differentiation suggests that there are human diseases resulting from defects in glycosphingolipid synthesis. In addition, the same cellular differentiation processes may be affected by defects in the degradation of glycosphingolipids. At the cellular level, the pathology of glycosphingolipid storage diseases is not completely understood. Cell biological studies on the intracellular fate and function of glycosphingolipids may open new ways to understand and defeat not only lipid storage diseases, but perhaps other diseases that have not been connected to glycosphingolipids so far.

scholarly journals Role of type 2A phosphatase regulatory subunit B56α in regulating cardiac responses to β-adrenergic stimulation in vivo

2018 ◽  
Vol 115 (3) ◽  
pp. 519-529 ◽  
Author(s):  
Sarah-Lena Puhl ◽  
Kate L Weeks ◽  
Alican Güran ◽  
Antonella Ranieri ◽  
Peter Boknik ◽  
...  
Keyword(s):  
Systolic Dysfunction ◽  
Heart Tissue ◽  
Left Ventricular ◽  
Regulatory Subunit ◽  
Adrenergic Stimulation ◽  
Hypertrophic Response ◽  
Cardiac Responses ◽  
Cardiac Phenotype ◽  
And Function

Abstract Aims B56α is a protein phosphatase 2A (PP2A) regulatory subunit that is highly expressed in the heart. We previously reported that cardiomyocyte B56α localizes to myofilaments under resting conditions and translocates to the cytosol in response to acute β-adrenergic receptor (β-AR) stimulation. Given the importance of reversible protein phosphorylation in modulating cardiac function during sympathetic stimulation, we hypothesized that loss of B56α in mice with targeted disruption of the gene encoding B56α (Ppp2r5a) would impact on cardiac responses to β-AR stimulation in vivo. Methods and results Cardiac phenotype of mice heterozygous (HET) or homozygous (HOM) for the disrupted Ppp2r5a allele and wild type (WT) littermates was characterized under basal conditions and following acute β-AR stimulation with dobutamine (DOB; 0.75 mg/kg i.p.) or sustained β-AR stimulation by 2-week infusion of isoproterenol (ISO; 30 mg/kg/day s.c.). Left ventricular (LV) wall thicknesses, chamber dimensions and function were assessed by echocardiography, and heart tissue collected for gravimetric, histological, and biochemical analyses. Western blot analysis revealed partial and complete loss of B56α protein in hearts from HET and HOM mice, respectively, and no changes in the expression of other PP2A regulatory, catalytic or scaffolding subunits. PP2A catalytic activity was reduced in hearts of both HET and HOM mice. There were no differences in the basal cardiac phenotype between genotypes. Acute DOB stimulation induced the expected inotropic response in WT and HET mice, which was attenuated in HOM mice. In contrast, DOB-induced increases in heart rate were unaffected by B56α deficiency. In WT mice, ISO infusion increased LV wall thicknesses, cardiomyocyte area and ventricular mass, without LV dilation, systolic dysfunction, collagen deposition or foetal gene expression. The hypertrophic response to ISO was blunted in mice deficient for B56α. Conclusion These findings identify B56α as a potential regulator of cardiac structure and function during β-AR stimulation.

Abstract 19727: ROCK2 Mediates Browning of White Fat and Protects Against Obesity

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Phetcharat Chen ◽  
Christina Park ◽  
Eltayeb Karrar ◽  
Chaoyung Wang ◽  
James Liao
Keyword(s):  
Weight Gain ◽  
Body Temperature ◽  
Cold Exposure ◽  
Diet Induced Obesity ◽  
Therapeutic Benefits ◽  
White Adipocytes ◽  
Important Regulator ◽  
And Function ◽  
White Fat ◽  
Adipocyte Development

Background: The Rho-activated kinases (ROCK1 and ROCK2) are serine threonine kinases that are ubiquitously expressed with higher levels of ROCK2 compared to ROCK1 in adipocytes. Recent studies suggest that ROCK2 may be an important regulator of energy metabolism and obesity. However, its role in adipocyte development and function is unknown. Methods and Result: To determine the role of ROCK2 in adipocyte development and obesity, we generated adipocyte-specific deletion (ROCK2 adipoQ-/- ) and overexpression (CA-ROCK adipoQ+/+ ) of ROCK2 in mice. Compared to control mice, CA-ROCK adipoQ+/+ mice exhibited increased browning of inguinal white adipose tissue (iWAT). Indeed, immunohistochemical staining of iWAT in CA-ROCK adipoQ+/+ mice showed that UCP1 was upregulated. Furthermore, CA-ROCK adipoQ+/+ mice on high fat diet were resistant to weight gain and obesity for up to 18 weeks. This is in contrast to ROCK2 adipoQ-/- mice, which developed more weight gain or obesity than control mice. To determine the physiological effects of ROCK2 on browning of iWAT, control and ROCK2 adipoQ-/- mice were exposed to 4°C for 1 week. In control mice, cold exposure increased ROCK2 activity and lead to browning of iWAT. However, the iWAT in ROCK2 adipoQ-/- mice failed to undergo browning. Analysis of gene expression in iWAT demonstrated increased UCP1 and mitochondria proteins in control but not ROCK2 adipoQ-/- mice. Thermal imaging revealed that ROCK2 adipoQ-/- mice were unable to maintain basal body temperature after prolonged cold exposure. In contrast, the heat map of the CA-ROCK adipoQ+/+ mice showed an elevation of body temperature, particularly in areas of iWAT as compared to that of control littermates. Conclusions: ROCK2 mediates the “browning” of white adipocytes and prevents the development of obesity through increased thermogenesis. These findings suggest that the activation of ROCK2 in adipocytes may have therapeutic benefits in preventing diet-induced obesity.

scholarly journals Empagliflozin improves chronic hypercortisolism-induced abnormal myocardial structure and cardiac function in mice

2020 ◽  
Vol 11 ◽  
pp. 204062232097483
Author(s):  
Qing-Qing Zhang ◽  
Guo-Qing Li ◽  
Yi Zhong ◽  
Jie Wang ◽  
An-Ning Wang ◽  
...  
Keyword(s):  
Myocardial Dysfunction ◽  
Sglt2 Inhibitor ◽  
Heart Tissue ◽  
Left Ventricular ◽  
Tissue Samples ◽  
Beneficial Effects ◽  
Reduced Body ◽  
Sodium Glucose Cotransporter ◽  
And Function ◽  
Visceral Adipose

Background: Chronic exposure to excess glucocorticoids is frequently associated with a specific cardiomyopathy. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has beneficial effects as it aids in the reduction of heart failure and cardiovascular mortality in hospitalized patients. The aim of this study was to investigate the effects of empagliflozin on chronic hypercortisolism-induced myocardial fibrosis and myocardial dysfunction in mice. Methods: Male C57BL/6J mice (6 weeks old) were randomized to control, corticosterone (CORT), and empagliflozin + CORT groups. After 4 weeks of administration, heart structure and function were evaluated by echocardiography, and peripheral blood and tissue samples were collected. Expressions of Ccl2, Itgax, Mrc1, and Adgre1 mRNA in heart tissue were evaluated by RT-PCR, and signal transducer and activator of transcription 3 (STAT3) and Toll-like receptor 4 (TLR4) protein expression were analyzed by Western blotting. Results: Empagliflozin effectively reduced body weight, liver triglyceride, visceral adipose volume, and uric acid in CORT-treated mice. Left ventricular hypertrophy and cardiac dysfunction were improved significantly, phosphorylated STAT3 and TLR4 were alleviated, and macrophage infiltration in the myocardium was inhibited after administration of empagliflozin in CORT-treated mice. Conclusion: Empagliflozin has beneficial effects on specific cardiomyopathy associated with CORT, and the results provide new evidence that empagliflozin might be a potential drug for the prevention of this disease.

Biosynthesis and Function of Membrane Lipids

2014 ◽  
pp. 411-421 ◽  
Author(s):  
Diego de Mendoza ◽  
Roberto Grau ◽  
John E. Cronan
Keyword(s):  
Membrane Lipids ◽  
And Function

scholarly journals Mutations in PCYT2 disrupt etherlipid biosynthesis and cause a complex hereditary spastic paraplegia

Brain ◽  
2019 ◽  
Vol 142 (11) ◽  
pp. 3382-3397 ◽  
Author(s):  
Frédéric M Vaz ◽  
John H McDermott ◽  
Mariëlle Alders ◽  
Saskia B Wortmann ◽  
Stefan Kölker ◽  
...  
Keyword(s):  
Hereditary Spastic Paraplegia ◽  
Membrane Lipids ◽  
Cerebellar Atrophy ◽  
Global Developmental Delay ◽  
Mrna Levels ◽  
Spastic Paraplegia ◽  
Protein Levels ◽  
And Function ◽  
Lipid Abnormalities ◽  
The Brain

Abstract CTP:phosphoethanolamine cytidylyltransferase (ET), encoded by PCYT2, is the rate-limiting enzyme for phosphatidylethanolamine synthesis via the CDP-ethanolamine pathway. Phosphatidylethanolamine is one of the most abundant membrane lipids and is particularly enriched in the brain. We identified five individuals with biallelic PCYT2 variants clinically characterized by global developmental delay with regression, spastic para- or tetraparesis, epilepsy and progressive cerebral and cerebellar atrophy. Using patient fibroblasts we demonstrated that these variants are hypomorphic, result in altered but residual ET protein levels and concomitant reduced enzyme activity without affecting mRNA levels. The significantly better survival of hypomorphic CRISPR-Cas9 generated pcyt2 zebrafish knockout compared to a complete knockout, in conjunction with previously described data on the Pcyt2 mouse model, indicates that complete loss of ET function may be incompatible with life in vertebrates. Lipidomic analysis revealed profound lipid abnormalities in patient fibroblasts impacting both neutral etherlipid and etherphospholipid metabolism. Plasma lipidomics studies also identified changes in etherlipids that have the potential to be used as biomarkers for ET deficiency. In conclusion, our data establish PCYT2 as a disease gene for a new complex hereditary spastic paraplegia and confirm that etherlipid homeostasis is important for the development and function of the brain.

Membrane proteins: is the future disc shaped?

2016 ◽  
Vol 44 (4) ◽  
pp. 1011-1018 ◽  
Author(s):  
Sarah C. Lee ◽  
Naomi L. Pollock
Keyword(s):  
Membrane Proteins ◽  
Maleic Acid ◽  
Membrane Lipids ◽  
Biological Membranes ◽  
Structure And Function ◽  
Amphiphilic Copolymer ◽  
New Approach ◽  
Analysis Techniques ◽  
Lipid Particles ◽  
And Function

The use of styrene maleic acid lipid particles (SMALPs) for the purification of membrane proteins (MPs) is a rapidly developing technology. The amphiphilic copolymer of styrene and maleic acid (SMA) disrupts biological membranes and can extract membrane proteins in nanodiscs of approximately 10 nm diameter. These discs contain SMA, protein and membrane lipids. There is evidence that MPs in SMALPs retain their native structures and functions, in some cases with enhanced thermal stability. In addition, the method is compatible with biological buffers and a wide variety of biophysical and structural analysis techniques. The use of SMALPs to solubilize and stabilize MPs offers a new approach in our attempts to understand, and influence, the structure and function of MPs and biological membranes. In this review, we critically assess progress with this method, address some of the associated technical challenges, and discuss opportunities for exploiting SMA and SMALPs to expand our understanding of MP biology.

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