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Ferric Reductases in Candida albicans: Expression and Regulation

By Rose Elizabeth Jeeves


Candida albicans is an opportunistic fungal pathogen of humans causing superficial\ud mucosal infections and more serious systemic infections in immunocompromised\ud individuals. It is found in both yeast and hyphal forms at sites of infection. In the\ud human body levels of iron are extremely low, and an invading organism needs a way of\ud sequestering iron. In C. albicans there is a high affinity iron uptake system in which\ud iron is first reduced to the soluble ferrous form by ferric reductases. Reduced iron is\ud then taken up into the cell by a complex of a multicopper oxidase protein with an iron\ud transport protein. Multicopper oxidase proteins require copper to function and so high\ud affinity iron and copper uptake is inextricably linked. It has previously been demonstrated that CaFre10p is the major cell surface ferric and\ud cupric reductase. It is shown here that CaFre7p also makes a significant contribution to\ud cell surface ferric and cupric reductase activity. However, whereas CaFRE10 is\ud regulated in response to iron levels, CaFRE7 is regulated in a copper responsive\ud manner. The CaFRE10 gene is regulated by the GATA-type transcriptional repressor\ud Sfu1p and CaFRE7 is not. We show that in a mutant containing a deletion of SFU1 the\ud expression of the major iron transport protein CaFTR1 is increased and there is a\ud corresponding increase in radioactive iron uptake. It is also shown here for the first\ud time that expression of CaFRE10 and CaFRE7 is lower in hyphae compared to yeast\ud and that this leads to a corresponding decrease in cell surface ferric, but not cupric\ud reductase activity. This shows for the first time that two important virulence\ud determinants, the acquisition of iron and the morphological form of C. albicans, are\ud linked

Publisher: University of Leicester
Year: 2009
OAI identifier:

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  1. (2002). A C-terminal domain of the membrane copper pump
  2. (1999). A copper-sensing transcription factor regulates iron uptake genes in Schizosaccharomyces pombe.
  3. (2004). A docking approach to the study of copper trafficking proteins; interaction between metallochaperones and soluble domains of copper ATPases.
  4. (2004). A family of Candida cell surface haem-binding proteins involved in haemin and haemoglobin-iron utilization.
  5. (2007). A GATA-type transcription factor regulates expression of the high-affinity iron uptake system in the methylotrophic yeast Pichia pastoris.
  6. (2000). A high-affinity iron permease essential for Candida albicans virulence.
  7. (2005). A humancurated annotation of the Candida albicans genome.
  8. (1999). A multicopper oxidase gene from Candida albicans: cloning, characterization and disruption.
  9. (1996). A permease-oxidase complex involved in high-affinity iron uptake in yeast.
  10. (1990). A rapid and simple method for preparation of RNA from Saccharomyces cerevisiae.
  11. (1992). A role for complement receptor-like molecules in iron acquisition by Candida albicans.
  12. (2001). A second iron-regulatory system in yeast independent of
  13. (1984). A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity".
  14. (2006). A transcription factor cascade involving Fep1 and the CCAAT-binding factor Php4 regulates gene expression in response to iron deficiency in the fission yeast Schizosaccharomyces pombe.
  15. (1999). Acquisition, transport, and storage of iron by pathogenic fungi.
  16. (2005). Activation of the iron regulon by the yeast Aft1/Aft2 transcription factors depends on mitochondrial but not cytosolic iron-sulfur protein biogenesis.
  17. (2003). Adaptation to environmental pH in Candida albicans and its relation to pathogenesis.
  18. (2004). An efficiently regulated promoter system for Cryptococcus neoformans utilizing the CTR4 promoter.
  19. (2008). An endocytic mechanism for haemoglobin-iron acquisition in Candida albicans.
  20. (2004). An ER packaging chaperone determines the amino acid uptake capacity and virulence of Candida albicans.
  21. (1997). An oxidase-permease-based iron transport system in Schizosaccharomyces pombe and its expression in Saccharomyces cerevisiae.
  22. (2001). Attenuation of virulence and changes in morphology in Candida albicans by disruption of the N-acetylglucosamine catabolic pathway.
  23. (1970). Calcium-dependent bacteriophage DNA infection.
  24. (2000). Candida albicans CFL1 encodes a functional ferric reductase activity that can rescue a Saccharomyces cerevisiae fre1 mutant.
  25. (2007). Candida albicans drug resistance another way to cope with stress.
  26. (2008). Candida albicans ferric reductases are differentially regulated in response to distinct forms of iron limitation by the Rim101 and CBF transcription factors.
  27. (1996). Candida albicans has a cell-associated ferric-reductase activity which is regulated in response to levels of iron and copper.
  28. (2005). Candida albicans hyphae have a Spitzenkorper that is distinct from the polarisome found in yeast and pseudohyphae.
  29. (2000). Candida albicans RIM101 pH response pathway is required for host-pathogen interactions.
  30. (2003). Candida albicans secreted aspartyl proteinases in virulence and pathogenesis. Microbiology and molecular biology reviews,
  31. (2004). Candida morphogenesis and host-pathogen interactions.
  32. (2001). CCC1 is a transporter that mediates vacuolar iron storage in yeast.
  33. (2005). Characteristics of candidaemia with Candida-albicans compared with non-albicans Candida species and predictors of mortality.
  34. (2002). Characterization and functional analysis of the siderophore-iron transporter CaArn1p in Candida albicans.
  35. (1999). Characterization of a haemolytic factor from Candida albicans.
  36. (2002). Characterization of DNA binding and the cysteine rich region of SRE, a GATA factor in Neurospora crassa involved in siderophore synthesis.
  37. (2002). Characterization of iron-binding motifs in Candida albicans high-affinity iron permease CaFtr1p by site-directed mutagenesis.
  38. (2003). Characterization of the Aspergillus nidulans transporters for the siderophores enterobactin and triacetylfusarinine C.
  39. (2001). Characterization of the binding interface between the copper chaperone Atx1 and the first cytosolic domain of Ccc2 ATPase.
  40. (1997). Characterization of the Fet4 protein of yeast. Evidence for a direct role in the transport of iron.
  41. (2000). Characterization of the Saccharomyces cerevisiae high affinity copper transporter Ctr3.
  42. (2002). Chemistry for an essential biological process: the reduction of ferric iron. Biometals: an international journal on the role of metal ions in biology, biochemistry,
  43. (2000). CIp10, an efficient and convenient integrating vector for Candida albicans.
  44. (2004). Cloning and functional characterization of the Rhizopus oryzae high affinity iron permease (rFTR1) gene.
  45. (2001). Cloning of Pichia pastoris Fet3: insights into the high affinity iron uptake system.
  46. (2002). Combinatorial control of yeast FET4 gene expression by iron, zinc, and oxygen.
  47. (2005). Contributions of hyphae and hypha-coregulated genes to Candida albicans virulence.
  48. (2005). Coordinated remodeling of cellular metabolism during iron deficiency through targeted mRNA degradation.
  49. (1947). Copper and iron in the blood serum of dairy cows.
  50. (2002). Copper chaperones: personal escorts for metal ions.
  51. (1998). Copper differentially regulates the activity and degradation of yeast Mac1 transcription factor.
  52. (2006). Copper induces cytoplasmic retention of fission yeast transcription factor cuf1.
  53. (2002). Copper ion-sensing transcription factor Mac1p post-translationally controls the degradation of its target gene product Ctr1p.
  54. (1996). Copper-dependent degradation of the Saccharomyces cerevisiae plasma membrane copper transporter Ctr1p in the apparent absence of endocytosis.
  55. (2004). Copper-dependent proteinprotein interactions studied by yeast two-hybrid analysis.
  56. (1997). Copper-specific transcriptional repression of yeast genes encoding critical components in the copper transport pathway.
  57. (2007). Crm1-mediated nuclear export of the Schizosaccharomyces pombe transcription factor Cuf1 during a shift from low to high copper concentrations.
  58. (2004). Cterminal domain of the membrane copper transporter Ctr1 from Saccharomyces cerevisiae binds four Cu(I) ions as a cuprous-thiolate polynuclear cluster: sub-femtomolar Cu(I) affinity of three proteins involved in copper trafficking.
  59. (2002). Deletion of the copper transporter CaCCC2 reveals two distinct pathways for iron acquisition in Candida albicans.
  60. (1975). Detection of specific sequences among DNA fragments separated by gel electrophoresis.
  61. (2001). Development of Streptococcus thermophilus lacZ as a reporter gene for Candida albicans.
  62. (2006). Differential expression of genes involved in iron metabolism in Aspergillus fumigatus.
  63. (2005). Divergence of Stp1 and Stp2 transcription factors in Candida albicans places virulence factors required for proper nutrient acquisition under amino acid control. Molecular and cellular biology,
  64. (1988). DNA damage and oxygen radical toxicity.
  65. (1979). Efficient transfer of large DNA fragments from agarose gels to diazobenzyloxymethyl-paper and rapid hybridization by using dextran sulfate.
  66. (2000). Energetics of copper trafficking between the Atx1 metallochaperone and the intracellular copper transporter,
  67. (2000). Evidence for mating of the "asexual" yeast Candida albicans in a mammalian host.
  68. (2007). Expression of Candida albicans Sfu1 in fission yeast complements the loss of the iron-regulatory transcription factor Fep1 and requires Tup co-repressors.
  69. (2003). Fep1 represses expression of the fission yeast Schizosaccharomyces pombe siderophore-iron transport system.
  70. (2002). Fep1, an iron sensor regulating iron transporter gene expression in Schizosaccharomyces pombe.
  71. (1992). Ferric iron reduction and iron assimilation in Saccharomyces cerevisiae.
  72. (1992). Ferric reductase of Saccharomyces cerevisiae: molecular characterization, role in iron uptake, and transcriptional control by iron.
  73. (2004). Ferrichrome in Schizosaccharomyces pombe--an iron transport and iron storage compound. Biometals : an international journal on the role of metal ions in biology, biochemistry,
  74. (1998). Ferrous iron uptake in Cryptococcus neoformans.
  75. (2000). Fine-resolution physical mapping of genomic diversity in Candida albicans.
  76. (2003). Fre1p Cu2+ reduction and Fet3p Cu1+ oxidation modulate copper toxicity in Saccharomyces cerevisiae.
  77. (1999). Functional analysis of the two zinc fingers of SRE, a GATA-type factor that negatively regulates siderophore synthesis in Neurospora crassa.
  78. (2006). Functional identification of highaffinity iron permeases from Fusarium graminearum. Fungal genetics and biology,
  79. (2000). Functional independence of the two cysteine-rich activation domains in the yeast Mac1 transcription factor.
  80. (2002). Fungal morphogenesis and host invasion.
  81. (2002). Fungi, dendritic cells and receptors: a host perspective of fungal virulence.
  82. (2002). Gcn4 co-ordinates morphogenetic and metabolic responses to amino acid starvation in Candida albicans.
  83. (2005). Gene Expression profiling and Phenotype Analyses of S. cerevisiae in Response to Changing Copper Reveals Six Genes with New Roles in Copper and Iron Metabolism.
  84. (1999). Genetic and physiologic characterization of ferric/cupric reductase constitutive mutants of Cryptococcus neoformans.
  85. (1990). Genetic evidence that ferric reductase is required for iron uptake in Saccharomyces cerevisiae.
  86. (2003). Global analysis of protein localization in budding yeast.
  87. (2003). Haemin uptake and use as an iron source by Candida albicans: role of CaHMX1-encoded haem oxygenase.
  88. (2004). Heme oxygenase in Candida albicans is regulated by hemoglobin and is necessary for metabolism of exogenous heme and hemoglobin to alpha-biliverdin.
  89. (1997). Hemin induces germ tube formation in Candida albicans.
  90. (2007). Hemoglobin is an effective inducer of hyphal differentiation in Candida albicans.
  91. (2004). Hemoglobin regulates expression of an activator of mating-type locus alpha genes in Candida albicans.
  92. (2007). Heterozygosity of genes on the sex chromosome regulates Candida albicans virulence.
  93. (2002). Host-microbe interactions: fungi invasive human fungal opportunistic infections.
  94. (2005). Hydrolytic enzymes as virulence factors of Candida albicans.
  95. (2007). Hyphal growth: a tale of motors, lipids, and the Spitzenkorper.
  96. (2006). Identification and Analysis of Ferric Reductase Genes in C. albicans. PhD edn.
  97. (2007). Identification and characterization of MFA1, the gene encoding Candida albicans a-factor pheromone.
  98. (2000). Identification and substrate specificity of a ferrichrome-type siderophore transporter
  99. (2001). Identification of a Candida albicans ferrichrome transporter and its characterization by expression in Saccharomyces cerevisiae.
  100. (1998). Identification of a copper-induced intramolecular interaction in the transcription factor Mac1 from Saccharomyces cerevisiae.
  101. (1999). Identification of a fungal triacetylfusarinine C siderophore transport gene (TAF1) in Saccharomyces cerevisiae as a member of the major facilitator superfamily. Biometals : an international journal on the role of metal ions in biology, biochemistry,
  102. (2001). Identification of a novel high affinity copper transport complex in the fission yeast Schizosaccharomyces pombe.
  103. (2007). Identification of a vacuole-associated metalloreductase and its role in Ctr2-mediated intracellular copper mobilization.
  104. (2002). Identification of members of the Aspergillus nidulans SREA regulon: genes involved in siderophore biosynthesis and utilization.
  105. (2007). In vivo and in vitro anaerobic mating in Candida albicans.
  106. (2005). Increased virulence and competitive advantage of a/alpha over a/a or alpha/alpha offspring conserves the mating system of Candida albicans.
  107. (2007). Infection-related gene expression in Candida albicans.
  108. (2007). Interaction of HapX with the CCAATbinding complex-a novel mechanism of gene regulation by iron. The EMBO journal,
  109. (2005). Interaction of pathogenic fungi with host cells: Molecular and cellular approaches.
  110. (2005). Iron acquisition from transferrin by Candida albicans depends on the reductive pathway.
  111. (2005). Iron and infection: the heart of the matter.
  112. (2004). Iron and microbial infection.
  113. (2004). Iron and proteins for iron storage and detoxification. Biometals : an international journal on the role of metal ions in biology, biochemistry,
  114. (1992). Iron assimilation in Cryptococcus neoformans.
  115. (2008). Iron Homeostasis: new players, newer insights.
  116. (2000). Iron metabolism in pathogenic bacteria.
  117. (2008). Iron transport & homeostasis mechanisms: Their role in health and disease.
  118. (1996). Ironregulated DNA binding by the AFT1 protein controls the iron regulon in yeast.
  119. (1993). Isogenic strain construction and gene mapping in Candida albicans.
  120. (1998). Isolation and characterization of a new gene, sre, which encodes a GATA-type regulatory protein that controls iron transport
  121. (1984). Isolation of the Candida albicans gene for orotidine-5'-phosphate decarboxylase by complementation of S. cerevisiae ura3 and E. coli pyrF mutations. Molecular & general genetics
  122. (1986). Laboratory Course Manual for Methods in Yeast Genetics. 1st edn.
  123. (2002). LacZ assays in yeast.
  124. (1975). Ligation of EcoRI endonuclease-generated DNA fragments into linear and circular structures.
  125. (1993). MAC1, a nuclear regulatory protein related to Cu-dependent transcription factors is involved in Cu/Fe utilization and stress resistance in yeast.
  126. (2002). Mechanisms of bacterial pathogenicity.
  127. (2001). Metal transporters that contribute copper to metallochaperones in Saccharomyces cerevisiae. Molecular genetics and genomics 265(5),
  128. Metalloregulation of FRE1 and FRE2 homologs in Saccharomyces cerevisiae.[erratum appears in
  129. MFalpha1, the gene encoding the alpha mating pheromone of Candida albicans.
  130. (2003). Microbial virulence results from the interaction between host and microorganism.
  131. (2004). Mobilization of intracellular copper stores by the ctr2 vacuolar copper transporter.
  132. (1997). Molecular analysis of a Penicillium chrysogenum GATA factor encoding gene (sreP) exhibiting significant homology to the Ustilago maydis urbs1 gene.
  133. (1994). Molecular characterization of a copper transport protein in S. cerevisiae: an unexpected role for copper in iron transport.
  134. (2000). Molecular evolution of the GATA family of transcription factors: conservation within the DNA-binding domain.
  135. (2003). Molecular genetics of fungal siderophore biosynthesis and uptake: the role of siderophores in iron uptake and storage.
  136. (1996). Molecular mechanism of thymidylate synthasecatalyzed reaction and interaction of the enzyme with 2- and/or 4-substituted analogues of dUMP and 5-fluoro-dUMP.
  137. (1997). Negative control of heavy metal uptake by the Saccharomyces cerevisiae BSD2 gene.
  138. (1997). Nonfilamentous C. albicans mutants are avirulent.
  139. (2004). Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clinical infectious diseases : an official publication of the Infectious Diseases
  140. (2005). Novel regulatory function for the CCAAT-binding factor in Candida albicans.
  141. (2001). NRG1 represses yeast-hypha morphogenesis and hypha-specific gene expression in Candida albicans. The EMBO journal,
  142. (2001). Old iron, young copper: from Mars to Venus.
  143. (1999). Opening the iron box: transcriptional metalloregulation by the Fur protein.
  144. (2000). Perspectives in inorganic structural biology: solution structures of metalloproteins.
  145. (2005). Post-transcriptional regulation of the yeast high affinity iron transport system.
  146. (2002). Posttranslational modifications of the AFET3 gene product: a component of the iron transport system in budding cells and mycelia of the yeast Arxula adeninivorans.
  147. (1994). Production of a hemolytic factor by Candida albicans.
  148. (1997). Purification and characterization of Fet3 protein, a yeast homologue of ceruloplasmin.
  149. (1999). Rapid hypothesis testing with Candida albicans through gene disruption with short homology regions.
  150. (2002). Reductive iron uptake by Candida albicans: role of copper, iron and the TUP1 regulator.
  151. (1999). Regulated expression of the Saccharomyces cerevisiae Fre1p/Fre2p Fe/Cu reductase related genes.
  152. (2002). Regulation of freA, acoA, lysF, and cycA expression by iron availability in Aspergillus nidulans.
  153. (1998). Regulation of high affinity iron uptake in the yeast Saccharomyces cerevisiae. Role of dioxygen and Fe.
  154. (1992). Regulation of iron uptake in Saccharomyces cerevisiae. The ferrireductase and Fe(II) transporter are regulated independently.
  155. (2002). Regulation of Saccharomyces cerevisiae FET4 by oxygen and iron.
  156. (2004). Regulatory networks affected by iron availability in Candida albicans.
  157. (2007). required for iron uptake in Fusarium graminearum.
  158. (2002). Resistance of Candida species to antifungal agents: molecular mechanisms and clinical consequences. The Lancet infectious diseases,
  159. (2007). Role of a CUF1/CTR4 copper regulatory axis in the virulence of Cryptococcus neoformans.
  160. (2000). Saccharomyces cerevisiae expresses three functionally distinct homologues of the nramp family of metal transporters. Molecular and cellular biology,
  161. (2002). Siderophore uptake by Candida albicans: effect of serum treatment and comparison with Saccharomyces cerevisiae.
  162. (2000). Siderophore-iron uptake in Saccharomyces cerevisiae. Identification of ferrichrome and fusarinine transporters.
  163. (1998). Siderophore-mediated iron uptake in Saccharomyces cerevisiae: the SIT1 gene encodes a ferrioxamine B permease that belongs to the major facilitator superfamily.
  164. (2001). Signaling through adenylyl cyclase is essential for hyphal growth and virulence in the pathogenic fungus Candida albicans.
  165. (2001). SREA is involved in regulation of siderophore biosynthesis, utilization and uptake in Aspergillus nidulans.
  166. (2000). Structural requirements for hemoglobin to induce fibronectin receptor expression in Candida albicans.
  167. (1983). Studies on transformation of Escherichia coli with plasmids.
  168. (2002). Subcellular localization of Aft1 transcription factor responds to iron status in Saccharomyces cerevisiae.
  169. (1951). Taxonomy of Yeast.
  170. (1997). The AFT1 transcriptional factor is differentially required for expression of highaffinity iron uptake genes in Saccharomyces cerevisiae.
  171. (2001). The ALS gene family of Candida albicans.
  172. (1999). The Aspergillus nidulans GATA factor SREA is involved in regulation of siderophore biosynthesis and control of iron uptake.
  173. (2004). The CaCTR1 gene is required for high-affinity iron uptake and is transcriptionally controlled by a copper-sensing transactivator encoded by CaMAC1.
  174. (2003). The Candida albicans CTR1 gene encodes a functional copper transporter.
  175. (2006). The Candida albicans mating type like locus [MTL] is not involved in chlamydospore formation. Medical mycology: official publication of the International Society for Human and
  176. (2006). The Cek1 and Hog1 mitogen-activated protein kinases play complementary roles in cell wall biogenesis and chlamydospore formation in the fungal pathogen Candida albicans.
  177. (2004). The diploid genome sequence of Candida albicans.
  178. (1997). The distal GATA sequences of the sid1 promoter of Ustilago maydis mediate iron repression of siderophore production and interact directly with Urbs1, a GATA family transcription factor.
  179. (2004). The distinct morphogenic states of Candida albicans.
  180. (2007). The effect of prostaglandin E2 on transcriptional responses of Candida albicans.
  181. (2000). The family of SMF metal ion transporters in yeast cells.
  182. (2000). The Fe(II) permease Fet4p functions as a low affinity copper transporter and supports normal copper trafficking in Saccharomyces cerevisiae.
  183. (1994). The FET4 gene encodes the low affinity Fe(II) transport protein of Saccharomyces cerevisiae.
  184. (1993). The fission yeast ferric reductase gene frp1+ is required for ferric iron uptake and encodes a protein that is homologous to the gp91-phox subunit of the human NADPH phagocyte oxidoreductase. Molecular and cellular biology,
  185. (2008). The hyphal-associated adhesin and invasion Als3 of Candida albicans mediates iron acquisition from host ferritin.
  186. (1999). The iron transporter Fth1p forms a complex with the Fet5 iron oxidase and resides on the vacuolar membrane.
  187. (2007). The metalloreductase Fre6p in Fe-efflux from the yeast vacuole.
  188. (1999). The molecular biology of the CCAAT-binding factor NF-Y.
  189. (2003). The proteome of Saccharomyces cerevisiae mitochondria.
  190. (2002). The response to iron deprivation in Saccharomyces cerevisiae: expression of siderophore-based systems of iron uptake.
  191. (2001). The role of the FRE family of plasma membrane reductases in the uptake of siderophore-iron in Saccharomyces cerevisiae.
  192. (1994). The Saccharomyces cerevisiae copper transport protein (Ctr1p). Biochemical characterization, regulation by copper, and physiologic role in copper uptake.
  193. (2004). The Schizosaccharomyces pombe corepressor Tup11 interacts with the iron-responsive transcription factor Fep1.
  194. (1997). The second finger of Urbs1 is required for iron-mediated repression of sid1 in Ustilago maydis.
  195. (2002). The siderophore iron transporter of Candida albicans (Sit1p/Arn1p) mediates uptake of ferrichrome-type siderophores and is required for epithelial invasion.
  196. (1997). The yeast FET5 gene encodes a FET3-related multicopper oxidase implicated in iron transport.
  197. (2001). Three cell wall mannoproteins facilitate the uptake of iron in Saccharomyces cerevisiae.
  198. (2005). through the cAMP-protein kinase A pathway to induce morphogenesis in Candida albicans.
  199. (2001). Transcript profiling in Candida albicans reveals new cellular functions for the transcriptional repressors
  200. (2004). Transcription of the yeast iron regulon does not respond directly to iron but rather to ironsulfur cluster biosynthesis.
  201. (2002). Transition metal transport in yeast.
  202. (1994). Two distinctly regulated genes are required for ferric reduction, the first step of iron uptake in Saccharomyces cerevisiae. Molecular and cellular biology,
  203. (2005). Unique aspects of gene expression during Candida albicans mating and possible G(1) dependency.
  204. (1987). Unique phenotype of opaque cells in the whiteopaque transition of Candida albicans.
  205. (1993). urbs1, a gene regulating siderophore biosynthesis in Ustilago maydis, encodes a protein similar to the erythroid transcription factor GATA-1. Molecular and cellular biology,
  206. (1987). White-opaque transition": a second high-frequency switching system in Candida albicans.
  207. (2008). Yap5 is an iron-responsive transcriptional activator that regulates vacuolar iron storage in yeast. Molecular and cellular biology,
  208. (2000). Yeast lacking Cu-Zn superoxide dismutase show altered iron homeostasis. Role of oxidative stress in iron metabolism.

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