Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brown adipose tissue (BAT) thermogenesis is an uncoupled ATPase-independent thermogenic mechanism. Ion transport by the Na,K pump is an ATPase-dependent thermogenic mechanism. Both have been proposed as mechanisms of altered energy expenditure during states of dietary energy surfeit and deficit. Our aim was to study these mechanisms during diet-induced obesity and weight loss. Over 36 weeks rats were fed lard- or tallow-based diets (63% energy as fat), or a control diet (12% energy as fat). During periods of restriction rats were fed 50% of the energy intake of controls in the form of a control diet. Several components of thermogenic response increased in rats eating high fat diets and decreased following dietary restriction. BAT activation occurred, particularly with a lard-based diet, as indicated by increased GDP binding and uncoupling protein (UCP) content. Na,K pump activity in thymocytes increased with the feeding of both high fat diets at some time points. Plasma T3 level increased in rats eating the lard-based diet and decreased with dietary restriction regardless of previous diet. Resting metabolic rate (RMR) of the animals was unchanged despite increases in these thermogenic components and was decreased in all groups following dietary restriction. Our results indicate a lack of any major role for activated BAT thermogenesis in mitigating the extent of the obesity induced by the high fat diets. The reasons for the differences in response to the two different sources of saturated fat, lard, and tallow, are not clear.
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PMID:Altered brown adipose tissue and Na,K pump activities during diet-induced obesity and weight loss in rats. 1635 May 67

Domain dynamics of the chicken gizzard smooth muscle myosin catalytic domain (heavy chain Cys-717) and regulatory domain (regulatory light chain Cys-108) were determined in the absence of nucleotides using saturation-transfer electron paramagnetic resonance. In unphosphorylated synthetic filaments, the effective rotational correlation times, tau(r), were 24 +/- 6 micros and 441 +/- 79 micros for the catalytic and regulatory domains, respectively. The corresponding amplitudes of motion were 42 +/- 4 degrees and 24 +/- 9 degrees as determined from steady-state phosphorescence anisotropy. These results suggest that the two domains have independent mobility due to a hinge between the two domains. Although a similar hinge was observed for skeletal myosin (Adhikari and Fajer (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 9643-9647. Brown et al. (2001) Biochemistry 40, 8283-8291), the latter displayed higher regulatory domain mobility, tau(r)= 40 +/- 3 micros, suggesting a smooth muscle specific mechanism of constraining regulatory domain dynamics. In the myosin monomers the correlation times for both domains were the same (approximately 4 micros) for both smooth and skeletal myosin, suggesting that the motional difference between the two isoforms in the filaments was not due to intrinsic variation of hinge stiffness. Heavy chain/regulatory light chain chimeras of smooth and skeletal myosin pinpointed the origin of the restriction to the heavy chain and established correlation between the regulatory domain dynamics with the ability of myosin to switch off but not to switch on the ATPase and the actin sliding velocity. Phosphorylation of smooth muscle myosin filaments caused a small increase in the amplitude of motion of the regulatory domain (from 24 +/- 4 degrees to 36 +/- 7 degrees ) but did not significantly affect the rotational correlation time of the regulatory domain (441 to 408 micros) or the catalytic domain (24 to 17 micros). These data are not consistent with a stable interaction between the two catalytic domains in unphosphorylated smooth muscle myosin filaments in the absence of nucleotides.
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PMID:Regulatory and catalytic domain dynamics of smooth muscle myosin filaments. 1668 94

Prevention of graft dysfunction is a major objective in transplantation medicine. Previous research on experimental heart transplantation indicated that treatment with the immunomodulatory peptide alpha-melanocyte stimulating hormone (alpha-MSH) improves histopathology, prolongs allograft survival, and reduces expression of the main tissue injury mediators. Because calcium-handling is critical in heart graft function, we determined the effects of transplantation injury and influences of alpha-MSH treatment on representative calcium regulatory proteins in rat heart allografts. Hearts from Brown Norway rats were transplanted heterotopically into MHC incompatible Lewis rats. Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), protein kinase C epsilon (PKC epsilon), sarcoplasmic/endoplasmic reticulum calcium-ATPase 2 (SERCA2a), arrestin-beta1 (Arrb1), cholinergic receptor M2 (Chrm2), and inositol 1,4,5-triphosphate receptor 1 (InsP(3)R1) were examined in: (1) non-transplanted donor hearts; (2) allografts from saline-treated rats; and (3) allografts from rats treated with the synthetic alpha-MSH analog Nle4-DPhe7-alpha-MSH (NDP-alpha-MSH) (100 microg i.p. every 12h). Transplantation injury was associated with severe reduction in calcium regulatory protein transcription and expression level. NDP-alpha-MSH administration partly reversed inhibition of protein transcription and almost completely prevented protein loss. Finally, because certain effects of cyclic 3'-5'-adenosine monophosphate (cAMP) signaling on calcium handling in cardiac myocytes depend on activation of exchange protein directly activated by cAMP 1 (Epac1), we determined Epac1 mRNA and protein expression in heart allografts. Transplantation injury markedly reduced Epac1. NDP-alpha-MSH treatment significantly preserved both Epac1 protein and mRNA in the allografts. Administration of alpha-MSH or related melanocortins could reduce transplantation-induced dysfunction through protection of heart calcium regulatory proteins.
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PMID:Treatment with alpha-melanocyte stimulating hormone preserves calcium regulatory proteins in rat heart allografts. 1817 58

Brown adipose tissue (BAT) is involved in rat and mice thermoregulation, and heat produced by BAT depends on the concerted action of thyroid hormones and catecholamines. Little is known about cold-induced thermogenesis in mammals that have little or no BAT, such as rabbits. In these animals, thermogenesis primarily occurs in skeletal muscle. In this work, we have studied the effect of cold acclimation (4 C for 10 d) in normal and hypothyroid rabbits. It is known that hypothyroid rats die after a few hours of cold exposure. We now show that, different from rats, hypothyroid rabbits sustain their body temperature and survive after 10 d cold exposure. When compared with rabbits kept at room temperature, the muscles of cold-exposed rabbits showed a dark red color characteristic of oxidative muscle fibers. According to this pattern, we observed that in both normal and hypothyroid rabbits, cold exposure promotes an increase in oxygen consumption by skeletal muscle mitochondria. Moreover, in red muscle, cold acclimation induces an increase in the expression and activity of sarcoplasmic reticulum Ca(2+) ATPase isoform 1 (SERCA1), one of the muscle enzymes involved in heat production. We conclude that rabbit cold tolerance is probably related to increased muscle oxidative metabolism and heat production by SERCA1 and that these changes are not completely dependent on normal thyroid function.
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PMID:Cold tolerance in hypothyroid rabbits: role of skeletal muscle mitochondria and sarcoplasmic reticulum Ca2+ ATPase isoform 1 heat production. 1870 25

Olga Petrivna Chepinoga, doctor of science (biology), senior scientific worker, was born on July 1, 1907, in Kyiv. She graduated from the 1st Kyiv Medical Institute (1927-1931). In 1931-1935 she worked at various medical institutions of Ukraine. In 1935 O. P. Chepinoga was employed by the Institute of Biochemistry of the National Academy of Sciences of the Ukr.SSR as a laborant, then as an assistant, junior and senior scientific worker. In 1940 O. P. Chepinoga defended a thesis for a Candidate's degree, and from 1941 she was given a rank of the senior scientific worker. During the Great Patriotic War she served in the armed forces of the Soviet Army (1941-1945) as a medical officer in the rank of captain. In 1944-1963 she worked at the Instutute of Biochemistry of the AS of the Ukr.SSR as a senior scientific worker, and in 1963-1965 headed the Laboratory of Nucleic Acids. In 1952 O. P. Chepinoga defended a thesis for Doctor's degree in biology On Biologic Role of Nucleic Acids. Investigations of O. P. Chepinoga were first devoted to oxidation processes in muscles in various physiologic conditions, physico-chemical properties of myosin and its ATPase activity. Since 1948 her scientific interests had been concentrating on studying the biologic role and metabolism of nucleic acids, their transformation in the organism in norm and in pathological states. She was the first to find that various proteins interacted with DNA molecule. The highest activity of DNAse and RNAse was revealed in the organs which permanently synthesize proteins (liver, spleen, pancreas). Under quantitative undifferentiated growth of malignant tumors (Brown-Pierse carcinoma and Crocker sarcoma) the great part belongs to the process of DNA disintegrations; DNAse activity increases considerably in the animal and human blood that is not observed at other somatic diseases and is of great diagnostic value. Considerable shifts in DNAse activity at various pathologies were not found. The enrichment of transport RNA with methyl groups with chemical modifications does not disturb the integrity of the polynucleotide chain and secondary structure but decreases their acceptor activity. O. P. Chepinoga has published 100 scientific works including one monograph and one handbook. Two candidate's theses were defended under her supervision. She was awarded the medals For Courage, For the Victory over Germany in the Great Patriotic War of 1941-1945 and numerous jubilee medals.
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PMID:[Ol'ha Petrivna Chepinoha--a founder of investigations of nucleic acids in biochemistry in Ukraine. To the 100th anniversary of birthday, 1.07.1907--27.04.1983]. 1914 Apr 60

Bovine spinal dysmyelination (BSD) is a recessive congenital neurodegenerative disease in cattle (Bos taurus) characterized by pathological changes of the myelin sheaths in the spinal cord. The occurrence of BSD is a longstanding problem in the American Brown Swiss (ABS) breed and in several European cattle breeds upgraded with ABS. Here, we show that the disease locus on bovine chromosome 11 harbors the SPAST gene that, when mutated, is responsible for the human disorder hereditary spastic paraplegia (HSP). Initially, SPAST encoding Spastin was considered a less likely candidate gene for BSD since the modes of inheritance as well as the time of onset and severity of symptoms differ widely between HSP and BSD. However, sequence analysis of the bovine SPAST gene in affected animals identified a R560Q substitution at a position in the ATPase domain of the Spastin protein that is invariant from insects to mammals. Interestingly, three different mutations in human SPAST gene at the equivalent position are known to cause HSP. To explore this observation further, we genotyped more than 3,100 animals of various cattle breeds and found that the glutamine allele exclusively occurred in breeds upgraded with ABS. Furthermore, all confirmed BSD carriers were heterozygous, while all affected calves were homozygous for the glutamine allele consistent with recessive transmission of the underlying mutation and complete penetrance in the homozygous state. Subsequent analysis of recombinant Spastin in vitro showed that the R560Q substitution severely impaired the ATPase activity, demonstrating a causal relationship between the SPAST mutation and BSD.
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PMID:Congenital bovine spinal dysmyelination is caused by a missense mutation in the SPAST gene. 1971 78

A modular total synthesis of the potent V-ATPase inhibitors archazolid A and B is reported. The convergent preparation was accomplished by late-stage diversification of joint intermediates. Key synthetic steps involve asymmetric boron-mediated aldol reactions, two consecutive Still-Gennari olefinations to set the characteristic (Z,Z)-diene system, a Brown crotyboration, and a diastereoselective aldol condensation of highly elaborate intermediates. For macrocyclization, both an HWE reaction and a Heck coupling were successfully employed to close the 24-membered macrolactone. During the synthetic campaign, a generally useful protocol for an E-selective Heck reaction of nonactivated alkenes and a method for the direct nucleophilic displacement of the Abiko-Masamune auxiliary with sterically hindered nucleophiles were developed. The expedient and flexible strategy will enable further SAR studies of the archazolids and more detailed evaluations of target-inhibitor interactions.
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PMID:Modular total synthesis of archazolid A and B. 1973 63

Aging skeletal muscle shows an increased time to peak force and relaxation and a decreased specific force, all of which could relate to changes in muscle Ca(2+) handling. The purpose of this study was to determine if Ca(2+)-handling protein content and function are decreased in senescent gastrocnemius muscle and if initiating a training program in late middle age (LMA, 29 mo old) could improve function in senescent (34- to 36-mo-old) muscle. LMA male Fischer 344 x Brown-Norway rats underwent 5-7 mo of treadmill training. Aging resulted in a decrease in maximal sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) activity and a decrease in Ca(2+) release rate but no change in Ca(2+) uptake rate. Efficiency of the Ca(2+) pump was increased with age, as was the content of SERCA2a. Training caused a further increase in SERCA2a content. Aging also caused an increase in protein carbonyl and reactive nitrogen species damage accumulation, and both further increased with training. Consistent with the increase in oxidative damage, heat shock protein 70 content was increased with age and further increased with training. Together, these results suggest that while initiating exercise training in LMA augments the age-related increase in expression of heat shock protein 70 and the more efficient SERCA2a isoform, it did not prevent the decrease in SERCA activity and exacerbated oxidative damage in senescent gastrocnemius muscle.
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PMID:Initiating treadmill training in late middle age offers modest adaptations in Ca2+ handling but enhances oxidative damage in senescent rat skeletal muscle. 2020 Jan 31

Brown adipose tissue (BAT) mitochondria thermogenesis is regulated by uncoupling protein 1 (UCP 1), GDP and fatty acids. In this report, we observed fusion of the endoplasmic reticulum (ER) membrane with the mitochondrial outer membrane of rats BAT. Ca(2+)-ATPase (SERCA 1) was identified by immunoelectron microscopy in both ER and mitochondria. This finding led us to test the Ca(2+) effect in BAT mitochondria thermogenesis. We found that Ca(2+) increased the rate of respiration and heat production measured with a microcalorimeter both in coupled and uncoupled mitochondria, but had no effect on the rate of ATP synthesis. The Ca(2+) concentration needed for half-maximal activation varied between 0.08 and 0.11 microM. The activation of respiration was less pronounced than that of heat production. Heat production and ATP synthesis were inhibited by rotenone and KCN. Liver mitochondria have no UCP1 and during respiration synthesize a large amount of ATP, produce little heat, GDP had no effect on mitochondria coupling, Ca(2+) strongly inhibited ATP synthesis and had little or no effect on the small amount of heat released. These finding indicate that Ca(2+) activation of thermogenesis may be a specific feature of BAT mitochondria not found in other mitochondria such as liver.
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PMID:Fusion of the endoplasmic reticulum and mitochondrial outer membrane in rats brown adipose tissue: activation of thermogenesis by Ca2+. 2020 53

Cadmium (Cd) is one of the most common toxic metals in water. To investigate the mechanism of Cd-induced apoptosis in the hepatopancreas, freshwater crabs Sinopotamon yangtsekiense were exposed to 0, 3.56, 7.12, 14.25, 28.49 and 56.98 mg/L Cd for 48 h. After a 48 h exposure, apoptosis and necroptosis were apparent in the group exposed to 28.49 mg/L Cd and only one case of necrosis was observed in the highest concentration of Cd. Electronic microscopy revealed chromatin condensation under nuclear membrane and mitochondrial membrane rupture in 14.25 and 28.49 mg/L Cd treatment groups. Brown colored apoptotic cells were detected with the TUNEL test in all Cd-treatment groups. The AI in 56.98 mg/L group was 1.4-fold greater than that in crabs exposed to 14.25mg/L Cd. Caspase-9, caspase-3, SDH and Ca(2+)-ATPase activities increased with increasing Cd concentration. However, the activities of caspase-8 and LDH did not change significantly compared with control group. These results implied that Cd induced apoptosis in the hepatopancreas occurs through a mitochondrial pathway.
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PMID:Mitochondrial pathway of apoptosis in the hepatopancreas of the freshwater crab Sinopotamon yangtsekiense exposed to cadmium. 2183 45


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