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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genetically obese rodents (ob/ob mice and fa/fa rats) and animals with dietary-induced thermogenesis represent two extremes in efficiency of energy retention: the former deposit dietary energy with high efficiency, whereas the later deposit dietary energy with low efficiency. These differences in efficiency of energy retention must, at the cellular level, be associated with changes in efficiency and/or rate of formation and/or utilization of ATP (and other high energy intermediates). Brown adipose tissue possesses a unique proton-conductance pathway that reduces the efficiency of ATP synthesis. It has been speculated that this pathway is suppressed in obese (ob/ob) mice and accelerated in rats with dietary-induced thermogenesis. Metabolic reactions that alter the rate of ATP utilization in animals include Na+, K+-ATPase and protein turnover. The concentration of Na+, K+-ATPase enzyme unites in skeletal muscle and liver of young adult obese (ob/ob) mice is lower than in tissues of young adult lean mice. There also appear to be alterations in protein turnover in certain tissues of obese (ob/ob) mice, but additional studies are required to determine if whole-body protein turnover is altered in these animals. Data are unavailable on either Na+, K+-ATPase or protein turnover in tissue of animals with dietary-induced thermogenesis. Continuation of studies in these areas should provide a metabolic basis for understanding individual variability in efficiency of energy retention.
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PMID:Efficiency of energy retention in genetically obese animals and in dietary-induced thermogenesis. 626 81

Brown adipose tissue is an important site of cold-induced nonshivering thermogenesis in many mammals. The plasma membrane-bound Na+-K+-ATPase has been shown to be significantly involved in this thermogenesis although its exact role is unknown at present. Evidence that coupling of oxidative phosphorylation to electron transport may become loosened during thermogenesis has prompted an investigation of potential roles of the Na+-K+ pump that would be compatible with altered respiratory coupling. One such role is that of modulating norepinephrine (NE)-induced lipolysis and hence provision of free fatty acids to the mitochondria. Under such conditions, inhibition of the pump would reduce NE-induced respiration by limiting substrate availability. If, in fact, the primary role of the pump in NE-induced thermogenesis is to facilitate substrate availability, provision of exogenous substrate should bypass this involvement and ameliorate the ouabain inhibition of respiration. In the present study, this possibility was examined by determining the effect of an exogenous substrate, butyrate, on the contribution of the Na+-K+ pump to NE-stimulated respiration of isolated hamster brown adipocytes. Although exogenous butyrate was able to serve as a substrate for brown adipocyte respiration, its presence had no significant effect on the ouabain sensitivity of NE-induced rates of oxygen consumption. That is, ouabain (1 mM) inhibited the NE-evoked thermogenesis of the adipocytes by 77.7 +/- 6.5% in the absence of butyrate (2 mM) and by 73.4 +/- 9.9% in its presence. It appears, therefore, that the contribution of the Na+-K+ membrane pump to brown fat thermogenesis does not simply reflect modulation of NE-evoked lipolysis.
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PMID:Effects of butyrate on ouabain-sensitive respiration of hamster brown adipocytes. 705 78

In rabbit alveolar macrophages, recovery of intracellular pH (pHi) from acid loads to pHi values > or = 6.8 at an extracellular pH (pHo) of 7.4 (nominal absence of CO2-HCO3-) is insensitive to amiloride, an inhibitor of Na(+)-H+ exchange, and abolished by bafilomycin A1, an inhibitor of vacuolar-type H(+)-ATPase [A. Bidani, S.E.S. Brown, T.A. Heming, R. Gurich, and T.D. Dubose, Jr. Am. J. Physiol. 257 (Cell Physiol. 26): C65-C76, 1989; A. Bidani and S. E. S. Brown. Am. J. Physiol. 259 (Cell Physiol. 28): C586-C598, 1990]. To further evaluate the roles of Na(+)-H+ exchange and H(+)-ATPase activity in pHi regulation in rabbit alveolar macrophages, we have investigated the effects of amiloride and bafilomycin over a greater range of pHi (6.3-7.0) and pHo (5.0-7.4). The results indicate that rabbit alveolar macrophages possess H(+)-ATPase and a Na(+)-H+ antiporter, both of which are activated by decrements in pHi. However, in all cases, H(+)-ATPase activity exclusively determined basal pHi and was the principal mechanism (> 50%) for pHi recovery from intracellular acid loads. The pHi set point for activation of Na(+)-H+ exchange was approximately 6.8 at pHo of 7.4 and approximately 6.5 at pHo of 6.8. Na(+)-H+ exchange did not contribute significantly to pHi recovery at acid-loaded pHi above these set points. At pHo of 7.4 and pHi > or = 6.8, pHi recovery displayed an activation energy of approximately 11,000 kcal/mol and temperature coefficient of approximately 2.1, which are consistent with an energy-dependent process (i.e., H+ pump).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:pHi regulation in alveolar macrophages: relative roles of Na(+)-H+ antiport and H(+)-ATPase. 802 57

The precise function of subunit B of the vacuolar H(+)-ATPase class is unknown, but it is essential for proton pumping. We have previously reported the DNA sequence and predicted protein sequence of the vacuolar ATPase subunit B for Candida tropicalis (Gu, H.H., Gallagher, M.J., Rupkey, S. and Dean, G.E. (1990) Nucleic Acids Res. 18, 7446). When the Candida gene was expressed in a Saccharomyce cerevisiae delta vat2 mutant from which the homologous gene had been deleted, viability and vacuolar acidification was restored to apparently wild-type levels. The predicted identity between these two proteins is 90%. We have searched for vacuolar ATPase subunits B from other species that might show a difference in function, when expressed in yeast, relative to the endogenous gene. We have cloned an apparently full-length 1.8-kb bovine subunit B cDNA from adrenal medulla that is about 1 kb shorter than the previously reported bovine brain cDNA (Puopolo, K., Kumamoto, C., Adachi, I., Magner, R. and Forgac, M. (1992) J. Biol. Chem. 267, 3696-3706; Nelson, R.D., Guo, X.L., Masood, K., Brown, D., Kalkbrenner, M. and Gluck, S. (1992) Proc. Natl. Acad. Sci. USA 89, 3541-3545), but nearly identical throughout the coding nucleotide and protein sequences; it is only 74% identical to the Saccharomyces subunit B protein sequence. Upon expression of this cDNA in two different delta vat2 deletion strains, the bovine cDNA restored function only partially, as judged by both viability at high pH and vacuolar acidification. Current work is aimed at determining which regions of the bovine protein require alteration in order to fully restore the delta vat2 strain to wild-type acidification, with the eventual goal of identifying interactive residues between subunit B and other proteins required for pump function.
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PMID:Saccharomyces cerevisiae expression of exogenous vacuolar ATPase subunits B. 837 94

The mechanisms whereby thyroid hormone increases heat production have been analyzed with emphasis in more recent developments. Thyroid hormone increases obligatory thermogenesis as a result of the stimulation of numerous metabolic pathways involved in development, remodeling, and delivery of energy to the tissues. In addition, thyroid hormone may specifically stimulate some thermogenic mechanisms selected during evolution of homeotherms (e.g., Na/K-ATPase, Ca2+ cycling in muscle). Thyroid hormone also plays an essential role in facultative thermogenesis interacting with the sympathetic nervous system (SNS) at various levels. Peripherally, thyroid hormone potentiates the effects of the SNS at the level of the adrenergic receptor and adenylyl cyclase complex as well as distal from this point. Synergistic interactions between T3 and cAMP on the regulation of gene expression have been described. Brown adipose tissue (BAT) T4-5'-deiodinase plays a central role in controlling heat production. When this enzyme is stimulated by norepinephrine in the euthyroid and hypothyroid condition, it provides high concentrations of T3 to BAT; inhibition by T4 in hyperthyroidism may limit brown fat thermogenic responses. Also, thyrotoxicosis uniquely reduces the expression of beta 3-adrenergic receptors in brown adipose tissue, and the increased obligatory thermogenesis of this condition, via afferent neural pathways, may reduce the hypothalamic stimulation of brown fat, providing additional mechanisms to limit brown adipose tissue thermogenesis in hyperthyroidism.
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PMID:Thyroid hormone control of thermogenesis and energy balance. 880 1

We previously identified transcripts encoding a G protein-coupled, extracellular calcium/polyvalent cation-sensing receptor, RaKCaR, in rat kidney (D. Riccardi, J. Park, W.-S. Lee, G. Gamba, E. M. Brown, and S. C. Hebert. Proc. Natl. Acad. Sci. USA 92:131-135, 1994), which was proposed to provide the mechanism for modulating a variety of renal functions in response to changes in extracellular Ca2+ (E. M. Brown. In: Handbook of Physiology. Bethesda, MD: Am. Physiol. Soc., 1992, sect. 8, vol. 2, chapt. 39, p. 1841-1916; and S. C. Hebert. Kidney Int. 50: 2129-2139, 1996). Here, we examine the cellular and regional distribution of receptor protein by immunofluorescence microscopy using a polyclonal antibody raised against a 22 amino acid region of the NH2 terminus of the receptor. The most intense fluorescence was seen at the basolateral border of cortical thick ascending limb cells. Basolateral staining for the receptor was also detected in medullary thick ascending limbs, in macula densa cells identified by costaining with antibody to brain nitric oxide synthase, NOS-B1, and in distal convoluted tubule cells distinguished by costaining for the apical thiazide-sensitive Na(+)-Cl- cotransporter. Apical anti-RaKCaR staining was detected at the base of the brush border of proximal tubules with decreasing intensity from S1 to S3 segments. In cortical collecting ducts, anti-RaKCaR staining was detected in some, but not all, type A intercalated cells identified by costaining with anti-H(+)-ATPase and anti-AE1 Cl-/HCO3- exchanger antibodies. The present study demonstrates that RaKCaR protein is expressed in many different nephron segments and that the polarity of receptor expression varies with cell type along the nephron. These results suggest potential roles for the extracellular Ca2+/ polyvalent cation-sensing receptor in responding to both circulating and urinary concentrations of divalent minerals and potentially other polyvalent cations (e.g., aminoglycoside antibiotics) to modulate nephron function.
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PMID:Localization of the extracellular Ca2+/polyvalent cation-sensing protein in rat kidney. 953 Feb 79

Interaction of many infectious agents with eukaryotic host cells is known to cause activation of the ubiquitous transcription factor nuclear factor kappaB (NF-kappaB) (U. Siebenlist, G. Franzoso, and K. Brown, Annu. Rev. Cell Biol. 10:405-455, 1994). Recently, we reported a biphasic pattern of NF-kappaB activation in cultured human umbilical vein endothelial cells consequent to infection with Rickettsia rickettsii, an obligate intracellular gram-negative bacterium and the etiologic agent of Rocky Mountain spotted fever (L. A. Sporn, S. K. Sahni, N. B. Lerner, V. J. Marder, D. J. Silverman, L. C. Turpin, and A. L. Schwab, Infect. Immun. 65:2786-2791, 1997). In the present study, we describe activation of NF-kappaB in a cell-free system, accomplished by addition of partially purified R. rickettsii to endothelial cell cytoplasmic extracts. This activation was rapid, reaching maximal levels at 60 min, and was dependent on the number of R. rickettsii organisms added. Antibody supershift assays using monospecific antisera against NF-kappaB subunits (p50 and p65) confirmed the authenticity of the gel-shifted complexes and identified both p50-p50 homodimers and p50-p65 heterodimers as constituents of the activated NF-kappaB pool. Activation occurred independently of the presence of endothelial cell membranes and was not inhibited by removal of the endothelial cell proteasome. Lack of involvement of the proteasome was further confirmed in assays using the peptide-aldehyde proteasome inhibitor MG 132. Activation was not ATP dependent since no change in activation resulted from addition of an excess of the unhydrolyzable ATP analog ATPgammaS, supplementation with exogenous ATP, or hydrolysis of endogenous ATP with ATPase. Furthermore, Western blot analysis before and after in vitro activation failed to demonstrate phosphorylation of serine 32 or degradation of the cytoplasmic pool of IkappaB alpha. This lack of IkappaB alpha involvement was supported by the finding that R. rickettsii can induce NF-kappaB activation in cytoplasmic extracts prepared from T24 bladder carcinoma cells and human embryo fibroblasts stably transfected with a superrepressor phosphorylation mutant of IkappaB alpha, rendering NF-kappaB inactivatable by many known signals. Thus, evidence is provided for a potentially novel NF-kappaB activation pathway wherein R. rickettsii may interact with and activate host cell transcriptional machinery independently of the involvement of the proteasome or known signal transduction pathways.
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PMID:Proteasome-independent activation of nuclear factor kappaB in cytoplasmic extracts from human endothelial cells by Rickettsia rickettsii. 957 57

GEF1 encodes the single CLC putative chloride channel in yeast. Its disruption leads to a defect in iron metabolism (Greene, J. R., Brown, N. H., DiDomenico, B. J., Kaplan, J., and Eide, D. (1993) Mol. Gen. Genet. 241, 542-553). Since disruption of GEF2, a subunit of the vacuolar H+-ATPase, leads to a similar phenotype, it was previously suggested that the chloride conductance provided by Gef1p is necessary for vacuolar acidification. We now show that gef1 cells indeed grow less well at less acidic pH. However, no defect in vacuolar acidification is apparent from quinacrine staining, and Gef1p co-localizes with Mnt1p in the medial Golgi. Thus, Gef1p may be important in determining Golgi pH. Systematic alanine scanning of the amino and the carboxyl terminus revealed several regions essential for Gef1p localization and function. One sequence (FVTID) in the amino terminus conforms to a class of sorting signals containing aromatic amino acids. This was further supported by point mutations. Alanine scanning of the carboxyl terminus identified a stretch of roughly 25 amino acids which coincides with the second CBS domain, a conserved protein motif recently identified. Mutations in the first CBS domain also destroyed proper function and localization. The second CBS domain can be transplanted to the amino terminus without loss of function, but could not be replaced by the corresponding domain of the homologous mammalian channel ClC-2.
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PMID:Golgi localization and functionally important domains in the NH2 and COOH terminus of the yeast CLC putative chloride channel Gef1p. 961 22

We have examined lipid peroxidation (LPO) and fatty acid acyl chain dynamics in synaptosomal membranes isolated from aged rat (Fischer 344 x Brown Norway F1 hybrids) brains, correlating these results with measurements of enzymatic activity of the synaptic plasma membrane Ca2(+)-ATPase (PMCA). Calcium-dependent ATPase activity in these membranes exhibits progressive decreases with a maximal loss of activity with age of approximately 35%. The sensitivity of this membrane-bound ion transporter to the lipid composition of the surrounding membrane, as well as the high abundance of oxidatively sensitive polyunsaturated fatty acyl chains in synaptosomal membranes, suggests that this age-related loss in catalytic turnover may result from LPO-mediated protein modification and/or changes in the physical structure of the bilayer. However, high-performance liquid chromatography analysis of 2,4-dinitrophenylhydrazone derivatives reveals no significant age-related increases in the content of reactive aldehydes (malondialdehyde, formaldehyde, acetaldehyde or acetone) which comprise breakdown products of lipid peroxidation. Electron paramagnetic resonance measurements employing 5- and 12-stearic acid spin labels with the nitroxide reporter groups at two depths in the bilayer were used to assess the fatty acyl chain dynamics (fluidity) of synaptosomal membranes. The resulting spectra demonstrate anisotropic lipid dynamics of two populations of lipids, i.e. lipids in direct association with membrane proteins (boundary lipids) and bulk lipids that do not directly associate with proteins. The nanosecond dynamics of both lipid populations is unaltered with age indicating that any compositional changes occurring with age are insufficient to result in alterations in bilayer fluidity relevant to PMCA activity. Thus, the observed age-related decline in PMCA activity may be explained by direct modification of membrane protein.
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PMID:Decrease in Ca-ATPase activity in aged synaptosomal membranes is not associated with changes in fatty acyl chain dynamics. 986 36

Food restriction (FR) exerts a variety of beneficial effects and may prolong life in both humans and animals. However, studies of its effects on the cortical brush border membrane (BBM) and basolateral membrane (BLM) lipid concentration, which may be pertinent to renal function, have not been reported in detail. We hypothesized that FR would decrease renal work and lower renal membrane lipid concentration. The changes in lipid concentration would be most dramatic in BBM because this membrane is the entry site for the recovery of filtered ions and nutrients. Young male Fischer 344 x Brown-Norway F1 rats consumed food ad libitum (AL) or were food-restricted (FR, 60% of AL consumption) for 6 wk. AL rats had higher fractional excretions of Na(+), K(+), and Cl(-) than did the FR group (P < 0.001). Renal Na,K-ATPase activity in AL rats was 100% higher than in FR rats (P < 0.001), reflecting greater renal work. The work required for renal proton secretion was lower in FR than in the AL rats. In FR rats, all BBM phospholipid concentrations (phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin) were approximately 50% lower than in the AL rats (P < 0.001). In the BLM, food restriction resulted only in lower phosphatidylcholine concentration, while the other phospholipids were unaffected. Plasma and renal membrane (BBM and BLM) cholesterol concentrations were significantly lower in FR than in AL rats. These results show that a nutritionally complete, but energy restricted, diet improves renal function. It also prevents renal membrane lipid deposition and decreases plasma cholesterol. Prolonged food restriction might attenuate the renal injury that occurs in obese humans as a consequence of insulin resistance and atherosclerosis.
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PMID:Food restriction beneficially affects renal transport and cortical membrane lipid content in rats. 1046 Feb 4


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