Alcohol and thiamine deficiency trigger differential mitochondrial transition pore opening mediating cellular death

Abstract

Accumulating evidence has shown that binge-type alcohol intake in mothers interferes with thiamine deficiency (TD) to promote the fetal alcohol syndrome (FAS). Developmental alcohol or TD exposures act either synergistically or separately to reproduce FAS features e.g. intrauterine growth retardation and related microcephaly characterized by extensive cellular death induced by one another neurotoxicant. However molecular and cellular mechanisms underlying apoptosis in both alcohol and TD toxicities are unknown. The current review addresses mechanisms of apoptosis underlying alcohol and TD toxicities for further understanding FAS pathology. This study indicates two different mitochondria pathways regulating cellular death: The first mechanism may engage alcohol which activates the c-subunit ring of the F0-ATP synthase to form MPT pore-dependent apoptosis; following the second mechanism, TD activates CyP-D translocation from mitochondrial matrix towards the mitochondrial inner membrane to form MPT pore-dependent necrosis. These studies shed light upon molecular and cellular mechanisms underlying apoptosis and necrosis in developemental brain disorders related to alcohol and thiamine deficiency, in hopes of developing new therapeutic strategies for FAS medication.

Disinhibited-Like Behavior Correlates With Frontal Cortex Damage in Alcohol-Induced Wernicke-Korsakoff Syndrome

“…In turn, ethanol and TD showed additive/synergistic toxicity on cellular death [59]. Recent studies indicate that TD can use caspase-3 classical pathway to amplify apoptosis as alcohol intoxication, although both alcohol and TD can induce cellular death by different pathways (reviewed in [60]. Taking into account our data, these observations may depend on the pattern of alcohol consumption and the degree of TD.…”

Disinhibition-Like Behavior Correlates with Frontal Cortex Damage in an Animal Model of Chronic Alcohol Consumption and Thiamine Deficiency

“…In turn, ethanol and TD showed additive and synergistic toxicity in cellular death [ 55 ]. Recent studies indicate that TD can use the caspase 3 classical pathway to amplify apoptosis as alcohol intoxication, although both alcohol and TD can induce cellular death by different pathways (reviewed in [ 56 ]). Taking into account our data, these observations may depend on the pattern of alcohol consumption and the degree of TD.…”

Effects of 17<i>β</i>-Estradiol on Dopamine D2 Receptors in Thiamine-Deficient Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight

“…Permanent increase in blood glucose during thiamine deficiency promoted diabetes mellitus [35] [36]. Indeed, Bâ [37] suggested that increasing extracellular glucose concentrations activated thiamine transportation from the bloodstream into both pancreatic beta cells for insulin releasing, and diverse or-gans tissues cells increasing mitochondrial ATP synthesis [38]. This process was expected to include thiamine membrane transporter coupled with a conventional G protein [39].…”