Induced inhibition of ischemic/hypoxic injury by APIP, a novel Apaf-1-interacting protein.

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Citation

Cho DH, Hong YM, Lee HJ, Woo HN, Pyo JO, Mak TW, Jung YK

Induced inhibition of ischemic/hypoxic injury by APIP, a novel Apaf-1-interacting protein.

J Biol Chem. 2004 Sep 17;279(38):39942-50. Epub 2004 Jul 15.

PubMed ID
15262985 [ View in PubMed
]
Abstract

We describe the isolation and characterization of a new apaf-1-interacting protein (APIP) as a negative regulator of ischemic injury. APIP is highly expressed in skeletal muscle and heart and binds to the CARD of Apaf-1 in competition with caspase-9. Exogenous APIP inhibits cytochrome c-induced activation of caspase-3 and caspase-9, and suppresses cell death triggered by mitochondrial apoptotic stimuli through inhibiting the downstream activity of cytochrome c released from mitochondria. Conversely, reduction of APIP expression potentiates mitochondrial apoptosis. APIP expression is highly induced in mouse muscle affected by ischemia produced by interruption of the artery in the hindlimb and in C2C12 myotubes created by hypoxia in vitro, and the blockade of APIP up-regulation results in TUNEL-positive ischemic damage. Furthermore, forced expression of APIP suppresses ischemia/hypoxia-induced death of skeletal muscle cells. Taken together, these results suggest that APIP functions to inhibit muscle ischemic damage by binding to Apaf-1 in the Apaf-1/caspase-9 apoptosis pathway.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Apoptotic protease-activating factor 1O14727Details