R M Uranga

Publications (3)6.24 Total impact

• Article: Differential participation of phospholipase A(2) isoforms during iron-induced retinal toxicity. Implications for age-related macular degeneration.

  G Rodríguez Diez, R M Uranga, M V Mateos, N M Giusto, G A Salvador
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  ABSTRACT: Both elevated iron concentrations and the resulting oxidative stress condition are common signs in retinas of patients with age-related macular degeneration (AMD). The role of phospholipase A(2) (PLA(2)) during iron-induced retinal toxicity was investigated. To this end, isolated retinas were exposed to increasing Fe(2+) concentrations (25, 200 or 800μM) or to the vehicle, and lipid peroxidation levels, mitochondrial function, and the activities of cytosolic PLA(2) (cPLA(2)) and calcium-independent PLA(2) (iPLA(2)) were studied. Incubation with Fe(2+) led to a time- and concentration-dependent increase in retinal lipid peroxidation levels whereas retinal cell viability was only affected after 60min of oxidative injury. A differential release of arachidonic acid (AA) and palmitic acid (PAL) catalyzed by cPLA(2) and iPLA(2) activities, respectively, was also observed in microsomal and cytosolic fractions obtained from retinas incubated with iron. AA release diminished as the association of cyclooxigenase-2 increased in microsomes from retinas exposed to iron. Retinal lipid peroxidation and cell viability were also analyzed in the presence of cPLA(2) inhibitor, arachidonoyl trifluoromethyl ketone (ATK), and in the presence of iPLA(2) inhibitor, bromoenol lactone (BEL). ATK decreased lipid peroxidation levels and also ERK1/2 activation without affecting cell viability. BEL showed the opposite effect on lipid peroxidation. Our results demonstrate that iPLA(2) and cPLA(2) are differentially regulated and that they selectively participate in retinal signaling in an experimental model resembling AMD.
  Neurochemistry International 06/2012; 61(5):749-58. · 2.86 Impact Factor
• Article: Effect of transition metals in synaptic damage induced by amyloid beta peptide.

  R M Uranga, N M Giusto, G A Salvador
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  ABSTRACT: The amyloid beta-peptide (Abeta), which is thought to be the major cause of Alzheimer's disease (AD), is known to be capable of aggregating in different states: soluble monomers and oligomers, and insoluble aggregates. The Abeta aggregation state as well as its toxicity has been related to the interaction between the peptide and transition metals such as iron and copper. However, this relationship, as well as the effects of Abeta on the synaptic endings, is not fully understood. The aggregation states of Abeta in the presence of iron and copper, as well as their effects on synaptic viability and signaling were investigated in this work. During acute incubation treatments (5 min-4 h), Abeta/metal impaired mitochondrial function to the same extent as has been observed with the metal alone. However, in the presence of Abeta/iron (10 and 50 muM), plasma membrane integrity was disrupted to a greater extent than when generated by either iron or Abeta alone, indicating that the membrane constitutes the first target of synaptic injury. Akt activation by Abeta/iron was evident after 5 min of incubation and was higher than that observed in the presence of the metal alone. This activation was barely detected after 4 h of incubation, demonstrating that there is no correlation between the extent of synaptic damage and the activation of this kinase. Extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation profile was different from that observed for Akt. Accordingly, the presence of Abeta/metal could differentially modulate the activity of these kinases. This work shows evidence of the initial events locally triggered at the synapse by Abeta and transition metals. As synapses have been proposed as the starting point of Abeta/metal-triggered events, the characterization of early mechanisms occurring in models that mimic AD could be important for the search of unexplored therapeutics tools.
  Neuroscience 10/2010; 170(2):381-9. · 3.38 Impact Factor
• Article: Effect of transition metals in synaptic damage induced by amyloid beta peptide

  R.M. Uranga, N.M. Giusto, G.A. Salvador
  [show abstract] [hide abstract]
  ABSTRACT: The amyloid β-peptide (Aβ), which is thought to be the major cause of Alzheimer's disease (AD), is known to be capable of aggregating in different states: soluble monomers and oligomers, and insoluble aggregates. The Aβ aggregation state as well as its toxicity has been related to the interaction between the peptide and transition metals such as iron and copper. However, this relationship, as well as the effects of Aβ on the synaptic endings, is not fully understood. The aggregation states of Aβ in the presence of iron and copper, as well as their effects on synaptic viability and signaling were investigated in this work. During acute incubation treatments (5 min–4 h), Aβ/metal impaired mitochondrial function to the same extent as has been observed with the metal alone. However, in the presence of Aβ/iron (10 and 50 μM), plasma membrane integrity was disrupted to a greater extent than when generated by either iron or Aβ alone, indicating that the membrane constitutes the first target of synaptic injury. Akt activation by Aβ/iron was evident after 5 min of incubation and was higher than that observed in the presence of the metal alone. This activation was barely detected after 4 h of incubation, demonstrating that there is no correlation between the extent of synaptic damage and the activation of this kinase. Extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation profile was different from that observed for Akt. Accordingly, the presence of Aβ/metal could differentially modulate the activity of these kinases. This work shows evidence of the initial events locally triggered at the synapse by Aβ and transition metals. As synapses have been proposed as the starting point of Aβ/metal-triggered events, the characterization of early mechanisms occurring in models that mimic AD could be important for the search of unexplored therapeutics tools.
  Neuroscience.