IN ABSENCE OF THE CELLULAR PRION PROTEIN, ALTERATIONS IN COPPER METABOLISM AND COPPER-DEPENDENT OXIDASE ACTIVITY AFFECT IRON DISTRIBUTION
Essential elements as copper and iron modulate a wide range of physiological functions. Their metabolism is strictly regulated by cellular pathways, since dysregulation of metal homeostasis is responsible for many detrimental effects. Neurodegenerative disorders such as Alzheimer’s disease, Parkinso...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2016-09-01
|
| Series: | Frontiers in Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnins.2016.00437/full |
| _version_ | 1818134339173482496 |
|---|---|
| author | Lisa Gasperini Elisa Meneghetti Giuseppe Legname Federico Benetti |
| author_facet | Lisa Gasperini Elisa Meneghetti Giuseppe Legname Federico Benetti |
| author_sort | Lisa Gasperini |
| collection | DOAJ |
| description | Essential elements as copper and iron modulate a wide range of physiological functions. Their metabolism is strictly regulated by cellular pathways, since dysregulation of metal homeostasis is responsible for many detrimental effects. Neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and prion diseases are characterized by alterations of metal ions. These neurodegenerative maladies involve proteins that bind metals and mediate their metabolism through not well-defined mechanisms. Prion protein, for instance, interacts with divalent cations via multiple metal-binding sites and it modulates several metal-dependent physiological functions, such as S-nitrosylation of NMDA receptors. In this work we focused on the effect of prion protein absence on copper and iron metabolism during development and adulthood. In particular, we investigated copper and iron functional values in serum and several organs such as liver, spleen, total brain and isolated hippocampus. Our results show that iron content is diminished in prion protein-null mouse serum, while it accumulates in liver and spleen. Our data suggest that these alterations can be due to impairments in copper-dependent cerulopalsmin activity which is known to affect iron mobilization. In prion protein-null mouse total brain and hippocampus, metal ion content shows a fluctuating trend, suggesting the presence of homeostatic compensatory mechanisms. However, copper and iron functional values are likely altered also in these two organs, as indicated by the modulation of metal-binding protein expression levels. Altogether, these results reveal that the absence of the cellular prion protein impairs copper metabolism and copper-dependent oxidase activity, with ensuing alteration of iron mobilization from cellular storage compartments. |
| first_indexed | 2024-12-11T09:07:03Z |
| format | Article |
| id | doaj.art-b72194b219364ec99ae4375af111568d |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-11T09:07:03Z |
| publishDate | 2016-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-b72194b219364ec99ae4375af111568d2022-12-22T01:13:36ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2016-09-011010.3389/fnins.2016.00437210766IN ABSENCE OF THE CELLULAR PRION PROTEIN, ALTERATIONS IN COPPER METABOLISM AND COPPER-DEPENDENT OXIDASE ACTIVITY AFFECT IRON DISTRIBUTIONLisa Gasperini0Elisa Meneghetti1Giuseppe Legname2Federico Benetti3SISSASISSASISSASISSAEssential elements as copper and iron modulate a wide range of physiological functions. Their metabolism is strictly regulated by cellular pathways, since dysregulation of metal homeostasis is responsible for many detrimental effects. Neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and prion diseases are characterized by alterations of metal ions. These neurodegenerative maladies involve proteins that bind metals and mediate their metabolism through not well-defined mechanisms. Prion protein, for instance, interacts with divalent cations via multiple metal-binding sites and it modulates several metal-dependent physiological functions, such as S-nitrosylation of NMDA receptors. In this work we focused on the effect of prion protein absence on copper and iron metabolism during development and adulthood. In particular, we investigated copper and iron functional values in serum and several organs such as liver, spleen, total brain and isolated hippocampus. Our results show that iron content is diminished in prion protein-null mouse serum, while it accumulates in liver and spleen. Our data suggest that these alterations can be due to impairments in copper-dependent cerulopalsmin activity which is known to affect iron mobilization. In prion protein-null mouse total brain and hippocampus, metal ion content shows a fluctuating trend, suggesting the presence of homeostatic compensatory mechanisms. However, copper and iron functional values are likely altered also in these two organs, as indicated by the modulation of metal-binding protein expression levels. Altogether, these results reveal that the absence of the cellular prion protein impairs copper metabolism and copper-dependent oxidase activity, with ensuing alteration of iron mobilization from cellular storage compartments.http://journal.frontiersin.org/Journal/10.3389/fnins.2016.00437/fullCopperIronprionOxidase activityEssential metals |
| spellingShingle | Lisa Gasperini Elisa Meneghetti Giuseppe Legname Federico Benetti IN ABSENCE OF THE CELLULAR PRION PROTEIN, ALTERATIONS IN COPPER METABOLISM AND COPPER-DEPENDENT OXIDASE ACTIVITY AFFECT IRON DISTRIBUTION Frontiers in Neuroscience Copper Iron prion Oxidase activity Essential metals |
| title | IN ABSENCE OF THE CELLULAR PRION PROTEIN, ALTERATIONS IN COPPER METABOLISM AND COPPER-DEPENDENT OXIDASE ACTIVITY AFFECT IRON DISTRIBUTION |
| title_full | IN ABSENCE OF THE CELLULAR PRION PROTEIN, ALTERATIONS IN COPPER METABOLISM AND COPPER-DEPENDENT OXIDASE ACTIVITY AFFECT IRON DISTRIBUTION |
| title_fullStr | IN ABSENCE OF THE CELLULAR PRION PROTEIN, ALTERATIONS IN COPPER METABOLISM AND COPPER-DEPENDENT OXIDASE ACTIVITY AFFECT IRON DISTRIBUTION |
| title_full_unstemmed | IN ABSENCE OF THE CELLULAR PRION PROTEIN, ALTERATIONS IN COPPER METABOLISM AND COPPER-DEPENDENT OXIDASE ACTIVITY AFFECT IRON DISTRIBUTION |
| title_short | IN ABSENCE OF THE CELLULAR PRION PROTEIN, ALTERATIONS IN COPPER METABOLISM AND COPPER-DEPENDENT OXIDASE ACTIVITY AFFECT IRON DISTRIBUTION |
| title_sort | in absence of the cellular prion protein alterations in copper metabolism and copper dependent oxidase activity affect iron distribution |
| topic | Copper Iron prion Oxidase activity Essential metals |
| url | http://journal.frontiersin.org/Journal/10.3389/fnins.2016.00437/full |
| work_keys_str_mv | AT lisagasperini inabsenceofthecellularprionproteinalterationsincoppermetabolismandcopperdependentoxidaseactivityaffectirondistribution AT elisameneghetti inabsenceofthecellularprionproteinalterationsincoppermetabolismandcopperdependentoxidaseactivityaffectirondistribution AT giuseppelegname inabsenceofthecellularprionproteinalterationsincoppermetabolismandcopperdependentoxidaseactivityaffectirondistribution AT federicobenetti inabsenceofthecellularprionproteinalterationsincoppermetabolismandcopperdependentoxidaseactivityaffectirondistribution |