MAPKs mediate the activation of cytosolic phospholipase A2 by amyloid β(25-35) peptide in bovine retina pericytes

Ambra Nicotra, Gabriella Lupo, Giovanni Giurdanella, Carmelina D. Anfuso, Nicolò Ragusa, Cataldo Tirolo, Bianca Marchetti, Mario Alberghina

Research output: Contribution to journalArticlepeer-review


We have previously shown that, in bovine retina pericytes, amyloid β(1-42) and its truncated form containing amino acids 25-35, after 24 h treatment, stimulate arachidonic acid (AA) release and phosphatidylcholine hydrolysis, by activation of both cytosolic (cPLA2) and Ca 2+-independent (iPLA2) phospholipase A2. A putative role for MAP kinases in this process emerged. Here we studied the role of the MAP-kinase family as well as both cPLA2 and iPLA2 mRNA expression by a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in the same sublethal model of amyloid-β (Aβ) damage to pericytes in vitro. Aβ(25-35) peptide evoked AA release as well as stimulated phosphorylation of ERK1/2, p38 MAPKs and cPLA2, but not c-Jun N-terminal kinase (JNK/SAPK). PD98059, an inhibitor of ERK-activating kinase MEK-1, and SB203580, an inhibitor of p38 protein kinase, abolished the stimulation of AA release and MAPK activities. In cells stimulated by Aβ(25-35) peptide, Western blotting and confocal microscopy analyses confirmed either an increase in the phosphorylated form of ERKs and p38 or their nuclear translocation. A complete inhibition of MAPK activation and AA release was also observed when pericytes were treated with GF109203X, a general PKC inhibitor, indicating the important role of both PKC and the two MAPKs in mediating the Aβ peptide response. Compared with samples untreated or treated with reverse Aβ(35-25) peptide, pretreatment with 50 μM Aβ(25-35) for 24 h significantly increased the level of constitutively expressed iPLA2 mRNA by 25%, which seems to depend on the activation of kinases. By contrast, the level of cPLA2 mRNA remained unchanged. Together, these data link either the stimulation of PKC-ERK-p38 cascades or PLA2 activity by Aβ peptide to prooxidant mechanism induced by amyloid, which may initially stimulate the cell reaction as well as metabolic repair, such as during inflammation.

Original languageEnglish
Pages (from-to)172-186
Number of pages15
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Issue number2-3
Publication statusPublished - Apr 15 2005


  • Amyloid β(25-35)
  • Cytosolic phospholipase A
  • ERK
  • MAPK
  • mRNA
  • p38
  • Pericyte

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Biophysics


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