PT  - JOURNAL ARTICLE
AU  - Donghui Zhu
AU  - Yinzhi Lai
AU  - Phullara B. Shelat
AU  - Chunhua Hu
AU  - Grace Y. Sun
AU  - James C-M. Lee
TI  - Phospholipases A<sub>2</sub> Mediate Amyloid-β Peptide-Induced Mitochondrial Dysfunction
AID  - 10.1523/JNEUROSCI.3505-06.2006
DP  - 2006 Oct 25
TA  - The Journal of Neuroscience
PG  - 11111--11119
VI  - 26
IP  - 43
4099  - http://www.jneurosci.org/content/26/43/11111.short
4100  - http://www.jneurosci.org/content/26/43/11111.full
SO  - J. Neurosci.2006 Oct 25; 26
AB  - Mitochondrial dysfunction has been implicated in the pathophysiology of Alzheimer's disease (AD) brains. To unravel the mechanism(s) underlying this dysfunction, we demonstrate that phospholipases A2 (PLA2s), namely the cytosolic and the calcium-independent PLA2s (cPLA2 and iPLA2), are key enzymes mediating oligomeric amyloid-β peptide (Aβ1–42)-induced loss of mitochondrial membrane potential and increase in production of reactive oxygen species from mitochondria in astrocytes. Whereas the action of iPLA2 is immediate, the action of cPLA2 requires a lag time of ∼12–15 min, probably the time needed for initiating signaling pathways for the phosphorylation and translocation of cPLA2 to mitochondria. Western blot analysis indicated the ability of oligomeric Aβ1–42 to increase phosphorylation of cPLA2 in astrocytes through the NADPH oxidase and mitogen-activated protein kinase pathways. The involvement of PLA2 in Aβ1–42-mediated perturbations of mitochondrial function provides new insights to the decline in mitochondrial function, leading to impairment in ATP production and increase in oxidative stress in AD brains.