Bcl-2 over-expression and activation of protein kinase C suppress the Trail-induced apoptosis in Jurkat T cells

Abstract

Trail, a tumor necrosis factor-related apoptosis-inducing ligand, is a novel potent endogenous activator of the cell death pathway through the activation of cell surface death receptors Trail-R1 and Trail-R2. Its role, like FasL in activation-induced cell death (AICD), has been demonstrated in immune system. However the mechanism of Trail induced apoptosis remains unclear. In this report, the recombinant Trail protein was expressed and purified. The apoptosis-inducing activity and the regulation mechanism of recombinant Trail on Jurkat T cells were explored in vitro. Trypan blue exclusion assay demonstrated that the recombinant Trail protein actively killed Jurkat T cells in a dose-dependent manner. Trail-induced apoptosis in Jurkat T cells were remarkably reduced by Bcl-2 over expression in Bcl-2 gene transfected cells. Treatment with PMA (phorbol 12-myristate 13-acetate), a PKC activator, suppressed Trail-induced apoptosis in Jurkat T cells. The inhibition of apoptosis by PMA was abolished by pretreatment with Bis, a PKC inhibitor. Taken together, it was suggested that Bcl-2 over-expression and PMA activated PKC actively down-regulated the Trail-mediated apoptosis in Jurkat T cell.

Intermittent hypoxia attenuates ischemia/reperfusion induced apoptosis in cardiac myocytes via regulating Bcl-2/Bax expression

“…Bcl-2, a 26 kDa protein, is predominantly localized to the cytoplasmic face of the mitochondria outer membrane, endoplasmic reticulum, and nuclear envelope. Bcl-2 seems to prevent apoptosis induced by many stimuli, for example, irradiation, FasL [26], TRAIL [27] and deprivation of growth factor, and it has been shown to suppress cytochrome c (cyt.c) efflux from mitochondria, inhibit calcium release from the endoplasmic reticulum [24,28,29]. Others have speculated that Bcl-2 regulates the generation of reactive oxygen radical since Bcl-2 is able to attenuate cell death induced by oxidative damaging agents [30,31].…”

Effective gene-viral therapy of leukemia by a new fiber chimeric oncolytic adenovirus expressing TRAIL: in vitro and in vivo evaluation

“…Our study revealed that the intrinsic mitochondrial pathway is also involved in SG235-TRAIL-induced apoptosis of leukemic cells evidenced by the activation of caspase-8 and caspase-9, decreased Bid, and dysfunction of mitochondria. Moreover, Bcl-2 family proteins are critical for the determination of sensitivity to TRAIL (28,29). Recent studies have shown that degradation of Mcl-1, a Bcl-2 family member, initiates mitochondrial apoptotic cascade (42).…”

Induction of mitochondrion-mediated apoptosis of CHO cells by tripchloro- lide

“…A number of stimuli, including stress, chemotherapeutic agents and UV radiation, appear to induce apoptosis via mitochondrial pathway [3,16,17]. In the present studies, the molecular changes related to the mitochondrion-regulated apoptotic pathway in TCtreated CHO cells were analyzed.…”