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The anabolic action of intermittent parathyroid hormone on cortical bone depends partly on its ability to induce nitric oxide‐mediated vasorelaxation in BALB/c mice
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S Gohin A Carriero C Chenu AA Pitsillides TR Arnett M Marenzana 《Cell biochemistry and function》2016,34(2):52-62
There is strong evidence that vasodilatory nitric oxide (NO) donors have anabolic effects on bone in humans. Parathyroid hormone (PTH), the only osteoanabolic drug currently approved, is also a vasodilator. We investigated whether the NO synthase inhibitor L‐NAME might alter the effect of PTH on bone by blocking its vasodilatory effect. BALB/c mice received 28 daily injections of PTH[1–34] (80 µg/kg/day) or L‐NAME (30 mg/kg/day), alone or in combination. Hindlimb blood perfusion was measured by laser Doppler imaging. Bone architecture, turnover and mechanical properties in the femur were analysed respectively by micro‐CT, histomorphometry and three‐point bending. PTH increased hindlimb blood flow by >30% within 10 min of injection (P < 0.001). Co‐treatment with L‐NAME blocked the action of PTH on blood flow, whereas L‐NAME alone had no effect. PTH treatment increased femoral cortical bone volume and formation rate by 20% and 110%, respectively (P < 0.001). PTH had no effect on trabecular bone volume in the femoral metaphysis although trabecular thickness and number were increased and decreased by 25%, respectively. Co‐treatment with L‐NAME restricted the PTH‐stimulated increase in cortical bone formation but had no clear‐cut effects in trabecular bone. Co‐treatment with L‐NAME did not affect the mechanical strength in femurs induced by iPTH. These results suggest that NO‐mediated vasorelaxation plays partly a role in the anabolic action of PTH on cortical bone. © 2016 The Authors. Cell Biochemistry and Function published by John Wiley & Sons, Ltd. 相似文献
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Nuclear gene trees and the phylogenetic relationships of the mangabeys (Primates: Papionini) 总被引:3,自引:1,他引:2
Phylogenetic relationships of mangabeys within the Old World monkey tribe
Papionini are inferred from analyses of nuclear DNA sequences from five
unlinked loci. The following conclusions are strongly supported, based on
congruence among trees derived for the five separate gene regions: (1)
mangabeys are polyphyletic within the Papionini; (2) Cercocebus is the
sister taxon to the genus Mandrillus; and (3) Lophocebus belongs to a clade
with Papio and Theropithecus, with Papio as its most likely sister taxon.
Morphologically based phylogenies positing mangabey monophyly were
evaluated by mapping the sequences for each locus on these trees. The data
seem to fit these trees poorly in both maximum-parsimony and likelihood
analyses. Incongruence among nuclear gene trees occurred in the
interrelationships among Lophocebus, Papio, and Theropithecus. Several
factors that may account for this incongruence are discussed, including
sampling error, random lineage sorting, and introgression.
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PPCMatrix: a PowerPC dotmatrix program to compare large genomic sequences against protein sequences 总被引:1,自引:0,他引:1
Summary : An interactive dotmatrix program for the MacOS was designed that
allows comparison of DNA to protein sequences using nested 3-frame
translations. Availability : Shareware, available at
http://copan.bioz.unibas.ch/software/ Contact : burglin@ubaclu. unibas.ch
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Evolution of eutherian cytochrome c oxidase subunit II: heterogeneous rates of protein evolution and altered interaction with cytochrome c 总被引:3,自引:1,他引:2
Cytochrome c oxidase subunit II (COII), encoded by the mitochondrial
genome, exhibits one of the most heterogeneous rates of amino acid
replacement among placental mammals. Moreover, it has been demonstrated
that cytochrome c oxidase has undergone a structural change in higher
primates which has altered its physical interaction with cytochrome c. We
collected a large data set of COII sequences from several orders of mammals
with emphasis on primates, rodents, and artiodactyls. Using phylogenetic
hypotheses based on data independent of the COII gene, we demonstrated that
an increased number of amino acid replacements are concentrated among
higher primates. Incorporating approximate divergence dates derived from
the fossil record, we find that most of the change occurred independently
along the New World monkey lineage and in a rapid burst before apes and Old
World monkeys diverged. There is some evidence that Old World monkeys have
undergone a faster rate of nonsynonymous substitution than have apes. Rates
of substitution at four-fold degenerate sites in primates are relatively
homogeneous, indicating that the rate heterogeneity is restricted to
nondegenerate sites. Excluding the rate acceleration mentioned above,
primates, rodents, and artiodactyls have remarkably similar nonsynonymous
replacement rates. A different pattern is observed for transversions at
four-fold degenerate sites, for which rodents exhibit a higher rate of
replacement than do primates and artiodactyls. Finally, we hypothesize
specific amino acid replacements which may account for much of the
structural difference in cytochrome c oxidase between higher primates and
other mammals.
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Molecular evolution of cytochrome c oxidase: rate variation among subunit VIa isoforms 总被引:3,自引:1,他引:2
Schmidt TR; Jaradat SA; Goodman M; Lomax MI; Grossman LI 《Molecular biology and evolution》1997,14(6):595-601
Cytochrome c oxidase (COX) consists of 13 subunits, 3 encoded in the
mitochondrial genome and 10 in the nucleus. Little is known of the role of
the nuclear-encoded subunits, some of which exhibit tissue-specific
isoforms. Subunit VIa is unique in having tissue-specific isoforms in all
mammalian species examined. We examined relative evolutionary rates for the
COX6A heart (H) and liver (L) isoform genes along the length of the
molecule, specifically in relation to the tissue-specific function(s) of
the two isoforms. Nonsynonymous (amino acid replacement) substitutions in
the COX6AH gene occurred more frequently than in the ubiquitously expressed
COX6AL gene. Maximum-parsimony analysis and sequence divergences from
reconstructed ancestral sequences revealed that after the ancestral COX6A
gene duplicated to yield the genes for the H and L isoforms, the sequences
encoding the mitochondrial matrix region of the COX VIa protein experienced
an elevated rate of nonsynonymous substitutions relative to synonymous
substitutions. This is expected for relaxed selective constraints after
gene duplication followed by purifying selection to preserve the
replacements with tissue-specific functions.
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Sherin Antony Peeyush Kumar T Jobin Mathew TR Anju CS Paulose 《Journal of biomedical science》2010,17(1):7
Glucose homeostasis in humans is an important factor for the functioning of nervous system. Hypoglycemia and hyperglycemia is found to be associated with central and peripheral nerve system dysfunction. Changes in acetylcholine receptors have been implicated in the pathophysiology of many major diseases of the central nervous system (CNS). In the present study we showed the effects of insulin induced hypoglycemia and streptozotocin induced diabetes on the cerebellar cholinergic receptors, GLUT3 and muscle cholinergic activity. Results showed enhanced binding parameters and gene expression of Muscarinic M1, M3 receptor subtypes in cerebellum of diabetic (D) and hypoglycemic group (D + IIH and C + IIH). α7nAchR gene expression showed a significant upregulation in diabetic group and showed further upregulated expression in both D + IIH and C + IIH group. AchE expression significantly upregulated in hypoglycemic and diabetic group. ChAT showed downregulation and GLUT3 expression showed a significant upregulation in D + IIH and C + IIH and diabetic group. AchE activity enhanced in the muscle of hypoglycemic and diabetic rats. Our studies demonstrated a functional disturbance in the neuronal glucose transporter GLUT3 in the cerebellum during insulin induced hypoglycemia in diabetic rats. Altered expression of muscarinic M1, M3 and α7nAchR and increased muscle AchE activity in hypoglycemic rats in cerebellum is suggested to cause cognitive and motor dysfunction. Hypoglycemia induced changes in ChAT and AchE gene expression is suggested to cause impaired acetycholine metabolism in the cerebellum. Cerebellar dysfunction is associated with seizure generation, motor deficits and memory impairment. The results shows that cerebellar cholinergic neurotransmission is impaired during hyperglycemia and hypoglycemia and the hypoglycemia is causing more prominent imbalance in cholinergic neurotransmission which is suggested to be a cause of cerebellar dysfunction associated with hypoglycemia. 相似文献