The anti-apoptotic activity associated with phosphatidylinositol transfer protein α activates the MAPK and Akt/PKB pathway

Abstract

The conditioned medium (CM) from mouse NIH3T3 fibroblast cells overexpressing phosphatidylinositol transfer protein alpha (PI-TPalpha; SPIalpha cells) demonstrates an increased anti-apoptotic activity compared with CM from wild type NIH3T3 (wtNIH3T3) cells. As previously shown, the anti-apoptotic activity acts by activating a G protein-coupled receptor, most probably a cannabinoid 1 (CB1)-like receptor as the activity was blocked by both pertussis toxin and rimonabant [M. Schenning, C.M. van Tiel, D. Van Manen, J.C. Stam, B.M. Gadella, K.W. Wirtz and G.T. Snoek, Phosphatidylinositol transfer protein alpha regulates growth and apoptosis of NIH3T3 cells: involvement of a cannabinoid 1-like receptor, J. Lipid Res. 45 (2004) 1555-1564]. The CB1 receptor appears to be expressed in mouse fibroblast cells, at levels in the order SPIalpha>wtNIH3T3>SPIbeta cells (i.e. wild type cells overexpressing PI-TPbeta). Upon incubation of SPIbeta cells with the PI-TPalpha-dependent anti-apoptotic factors, both the ERK/MAP kinase and the Akt/PKB pathway are activated in a CB1 receptor dependent manner as shown by Western blotting. In addition, activation of ERK2 was also shown by EYFP-ERK2 translocation to the nucleus, as visualized by confocal laser scanning microscopy. The subsequent activation of the anti-apoptotic transcription factor NF-kappaB is in line with the increased resistance towards UV-induced apoptosis. On the other hand, receptor activation by CM from SPIalpha cells was not linked to phospholipase C activation as the YFP-labelled C2-domain of protein kinase C was not translocated to the plasma membrane of SPIbeta cells as visualized by confocal laser scanning microscopy.

NGF‐Dependent Activation of TrkA Pathway: A Mechanism for the Neuroprotective Effect of Troxerutin in D‐Galactose‐Treated Mice

“…ERK signaling pathway is one of the three mitogenactivated protein kinase (MAPK) cascades that play important roles in the regulation of cell proliferation, differentiation and survival. Evidence shows that phosphorylated ERK may phosphorylate a variety of substrates and promote cell survival (5,31,53). The present results suggested that NGF-activated TrkA mediated Akt and ERK phosphorylation, which could promote neuronal survival against oxidative damage.…”

“…Both Akt/PKB and ERK/MAPK are of tremendous importance for several neuronal key signaling events, including cell differentiation, proliferation and survival (53). In the present study, we investigated whether these pathways were involved in brain protection effects of troxerutin.…”

Staurosporine‐induced apoptosis in P388D1 macrophages involves both extrinsic and intrinsic pathways

“…Data are expressed as mean AE SD from three independent experiments performed in triplicate. Results showing statistically significant differences from control: *p < 0.05 and ***p < 0.001. phosphatidylserine synthases, phosphatidylinositol transfer protein alpha and anti-apoptotic protein BCL-xL (Chaturvedi et al, 2004;Rochette and Brash, 2008;Schenning et al, 2008;Yu et al, 2004). There are no reports of overexpression of these molecules in P388D1 macrophages.…”

“…fibroblasts, Chinese-hamster ovary cells and keratinocytes (Carvalho et al, 2008;Chaturvedi et al, 2004;Rochette and Brash, 2008;Schenning et al, 2008;Yu et al, 2004). This resistance is related to the overexpression of Fig.…”

Cannabinoid CB1 receptor inhibition decreases vascular smooth muscle migration and proliferation

“…Recent studies have reported that CB 1 inhibition in human peripheral blood mononulclear, human breast cancer cells, and NIH3T3 fibroblasts results in inhibition of the cell proliferation and migration and/or apoptosis mediated via inhibition of ERK1/2 and interrelated signaling pathways [20] [21] [22] [23]. CB 1 inhibition also attenuates doxorubicin-induced cell death in cardiomyocytes, which may also involve ERK1/2 activation [24].…”