Interactions of acetylcholinesterase with caveolin-1 and subsequently with cytochrome c are required for apoptosome formation

Abstract

Acetylcholinesterase (AChE) is emerging as an important component in leading to apoptosis. Our previous study demonstrated that silencing of the AChE gene blocked the interaction between cytochrome c and apoptotic protease-activating factor-1 (Apaf-1) in etoposide-induced apoptosis of HT-29 cells. We undertook this study to further dissect the molecular role of AChE in apoptosome formation. The present study elicited that small interfering RNA (siRNA) to cytochrome c gene blocked the interaction of AChE with Apaf-1, whereas siRNA to Apaf-1 gene did not block the interaction of AChE with cytochrome c, indicating that the interaction of AChE with cytochrome c is required for the interaction between cytochrome c and protease-activating factor-1. We further observed that AChE is localized to caveolae via interacting with caveolin-1 during apoptosis and that the disruption of caveolae prevented apoptosome formation. These data indicate that the interactions of AChE with caveolin-1 and subsequently with cytochrome c appear to be indispensable for apoptosome formation.

Acetylcholinesterase overexpression mediated by oncolytic adenovirus exhibited potent anti-tumor effect

“…Our data partially consistent with previous reports that AChE is required for apoptosome formation [31]. Other researches indicated that ACh stimulated the nicotinic acetylcholine receptor (nAChR) signaling which is pathologically over-activated in tumor [1].…”

The Caveolin-1 Connection to Cell Death and Survival

“…Moreover, AChE interacts with Caveolin-1 during apoptosis in events that precede apoptosome formation. While AChE plays a crucial role in promoting oligomerization of Apaf-1, Caveolin-1 appears neither to interact with cytochrome C nor with Apaf-1 [110].…”

Acetylcholinesterase is associated with a decrease in cell proliferation of hepatocellular carcinoma cells

“…In a non-synaptic context, the reports dealing with the altered expression of AChE in a wide range of tumor classes [13], along with the well-documented capacity of AChE to halt the cell cycle progression [14] and to promote apoptosis by facilitating the apoptosome assembly [15][16][17] raise the possibility that AChE collaborate to carcinogenesis through different pathways. The reports showing that AChE functions as a tumor growth suppressor in hepatocellular carcinoma [18,19] and in non-small cell lung cancer, in the latter via suppression by an AChE-targeted microRNA-212 [20] lend strong support to the relationship of AChE with tumorigenesis.…”