Ethanol promotes T cell apoptosis through the mitochondrial pathway

Abstract

SUMMARYClinical reports suggest that acute ethanol intoxication is often associated with lymphopenia. Previously, ethanol was reported to invoke thymocyte apoptosis. We studied the effect of ethanol on T cell apoptosis. In addition, we evaluated the molecular mechanism of ethanol-induced T cell apoptosis. Human T cells harvested from healthy subjects after an alcohol drinking binge showed enhanced T cell apoptosis (before, 0Á4 AE 0Á2% versus after, 19Á6 AE 2Á5% apoptotic lymphocytes/ field; P < 0Á001). In in vitro studies, ethanol in a concentration of 50 mM and higher enhanced the apoptosis of Jurkat cells. DNA isolated from ethanol-treated Jurkat cells displayed integer multiples of 180 base pairs. Ethanol decreased Jurkat cell expression of Bcl-2, whereas ethanol increased Jurkat cell expression of Bax. Jurkat cells treated with ethanol also showed translocation of cytochrome C into cytosol. Moreover, a caspase-9 inhibitor partially inhibited ethanol-induced Jurkat cell apoptosis. In in vivo studies, after binge drinking, T cell expression of Bcl-2 also decreased. In addition, binge drinking induced the cleavage of caspase-3, suggesting activation of caspase-3 in T cells. These results suggest that ethanol promotes T cell apoptosis through the activation of intrinsic or mitochondrial pathway.Excessive use of alcohol is a serious problem in our society. Its chronic use affects health in the form of cirrhosis, gastrointestinal haemorrhage, trauma and cancer. Moreover, chronic alcoholics are prone to develop bacterial infections.

Ethanol acts as a potent agent sensitizing colon cancer cells to the TRAIL‐induced apoptosis

“…It was reported that upon ethanol treatment, caspase activation, modulation of extracellular signal-regulated kinase 1/2 (ERK1/2) activity, changes in Bcl-2 family protein expression, increase in intracellular calcium ion concentration and DNA fragmentation occur [2][3][4]11]. Ethanol was also described to promote apoptosis through activation of the intrinsic or mitochondrial pathway as documented by an increased mitochondrial permeability transition, translocation of cytochrome c, and caspase-9 activation [1,4]. We demonstrated that human colon cancer HT-29 cells are relatively resistant to ethanol effects.…”

“…However, previous reports have demonstrated a role of ethanol in the apoptotic death of many cell types [1][2][3][4]. Apoptosis has also been shown to occur in both experimental and clinical alcoholic liver disease, but the signalling pathways remain not fully understood [5].…”

Involvement of Promyelocytic Leukemia Protein in the Ethanol-induced Apoptosis in Mouse Embryo Fibroblasts

“…1 3) Increased levels of ethanol and repeated exposures trigger apoptosis in hepatocytes, 1) astrocytes, 4) neurons, 5) T lymphocytes, 6) macrophages, 7) gastric mucosas, 8) and mouse embryoˆbroblasts (MEF), 9) leading to liver injury, neuro-behavioral problems, modulation of immune responses, and enhanced risk for cancer. Although the cellular spectrum of apoptosis induced by ethanol is well known, the signal transduction molecules involved in this process remain poorly dened.…”

Ethanol promotes cytotoxic effects of tumor necrosis factor-related apoptosis-inducing ligand through induction of reactive oxygen species in prostate cancer cells

“…Indeed, a critical role for ethanol in promoting apoptotic events in various cell lines and animal models has been well documented. [20][21][22][23][24][25][26][27][28][29] Also, ethanol stimulates the TRAIL-induced apoptosis in leukemic T-lymphocytes and colon cancer cells in vitro. 38,39 Despite these data, an interactive effect of ethanol and TRAIL in promoting PCa cell death has not been studied.…”

“…[10][11][12][13][14][15][16][17][18][19] Ethanol-induced apoptotic cell death has been well recognized in many cell types and animal models. [20][21][22][23][24] High concentrations of ethanol can effectively destroy hepatoma tumor as well as normal cells, whereas lower concentrations of ethanol selectively induces apoptosis in hepatoma tumor cells but not in normal hepatocytes. 25 Ethanol induces significant apoptosis of purkinje cells in the developing cerebellum.…”