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On the Cytoprotective Role of Ferritin in Macrophages and its Ability to Enhance Lysosomal Stability 总被引:3,自引:0,他引:3
Macrophages have a great capacity to take up (eg. by endocytosis and phagocytosis) exogenous sources of iron which could potentially become cytotoxic, particularly following the intralysosomal formation of low-molecular weight, redox active iron, and under conditions of oxidative stress. Following autophago-cytosis of endogenous ferritin/apoferritin, these compounds may serve as chelators of such lysosomal iron and counteract the occurrence of iron-mediated intralysosomal oxidative reactions. Such redox-reactions have been shown to lead to destabilisation of lysosomal membranes and result in leakage of damaging lysosomal contents to the cytosol. In this study we have shown: (i) human monocyte-derived macrophages to accumulate ferritin in response to iron exposure; (ii) iron to destabilise macrophage secondary lysosomes when the cells are exposed to H2O2; and (iii) endocytosed apoferritin to act as a stabiliser of the acidic vacuolar compartment of iron-loaded macrophages. While the endogenous ferritin accumulation which was induced by iron exposure was not sufficient to protect cells from the damaging effects of H2O2, exogenously added apoferritin, as well as the potent iron chelator desferrioxamine, afforded significant protection. It is suggested that intralysosomal formation of haemosiderin, from partially degraded ferritin, is a protective strategy to suppress intralysosomal iron-catalysed redox reactions. However, under conditions of severe macrophage lysosomal iron-overload, induction of ferritin synthesis is not enough to completely prevent the enhanced cytotoxic effects of H2O2. 相似文献
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Comparison of the evolutionary dynamics of symbiotic and housekeeping loci: a case for the genetic coherence of rhizobial lineages 总被引:6,自引:1,他引:5
In prokaryotes, lateral gene transfer across chromosomal lineages may be
mediated by plasmids, phages, transposable elements, and other accessory
DNA elements. However, the importance of such transfer and the evolutionary
forces that may restrict gene exchange remain largely unexplored in native
settings. In this study, tests of phylogenetic congruence are employed to
explore the range of horizontal transfer of symbiotic (sym) loci among
distinct chromosomal lineages of native rhizobia, the nitrogen-fixing
symbiont of legumes. Rhizobial strains isolated from nodules of several
host plant genera were sequenced at three loci: symbiotic nodulation genes
(nodB and nodC), the chromosomal housekeeping locus glutamine synthetase II
(GSII), and a portion of the 16S rRNA gene. Molecular phylogenetic analysis
shows that each locus generally subdivides strains into the same major
groups, which correspond to the genera Rhizobium, Sinorhizobium, and
Mesorhizobium. This broad phylogenetic congruence indicates a lack of
lateral transfer across major chromosomal subdivisions, and it contrasts
with previous studies of agricultural populations showing broad transfer of
sym loci across divergent chromosomal lineages. A general correspondence of
the three rhizobial genera with major legume groups suggests that host
plant associations may be important in the differentiation of rhizobial nod
and chromosomal loci and may restrict lateral transfer among strains. The
second major result is a significant incongruence of nod and GSII
phylogenies within rhizobial subdivisions, which strongly suggests
horizontal transfer of nod genes among congenerics. This combined evidence
for lateral gene transfer within, but not between, genetic subdivisions
supports the view that rhizobial genera are "reproductively isolated" and
diverge independently. Differences across rhizobial genera in the
specificity of host associations imply that the evolutionary dynamics of
the symbiosis vary considerably across lineages in native settings.
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