Protein Traffic Is an Intracellular Target in Alcohol Toxicity

Abstract

Eukaryotic cells comprise a set of organelles, surrounded by membranes with a unique composition, which is maintained by a complex synthesis and transport system. Cells also synthesize the proteins destined for secretion. Together, these processes are known as the secretory pathway or exocytosis. In addition, many molecules can be internalized by cells through a process called endocytosis. Chronic and acute alcohol (ethanol) exposure alters the secretion of different essential products, such as hormones, neurotransmitters and others in a variety of cells, including central nervous system cells. This effect could be due to a range of mechanisms, including alcohol-induced alterations in the different steps involved in intracellular transport, such as glycosylation and vesicular transport along cytoskeleton elements. Moreover, alcohol consumption during pregnancy disrupts developmental processes in the central nervous system. No single mechanism has proved sufficient to account for these effects, and multiple factors are likely involved. One such mechanism indicates that ethanol also perturbs protein trafficking. The purpose of this review is to summarize our understanding of how ethanol exposure alters the trafficking of proteins in different cell systems, especially in central nervous system cells (neurons and astrocytes) in adult and developing brains.

Nonstandard neutrino interactions in supernovae

“…In the top panel is the case of no NSI and one observes no flavor transformation until the neutrino reaches r ∼ 1000 km which is the location of the MSW H resonance. In the middle panel we switch on the NSI using δǫ n = −0.84 and ǫ 0 = 2.5 × 10 −4 and find a result similar to those of Esteban-Pretel, Tomàs, and Valle [37]. One observes a NSI-induced flavor conversion at r ∼ 40 km (which is the I resonance) and then another effect not usually seen in seen in the normal hierarchy which starts at r ∼ 150 km which we will show is the bipolar/nutation oscillations.…”

“…The effect of sterile neutrinos in supernovae has been considered on many occasions [14][15][16][17][18][19][20][21] and neutrino magnetic moments were studied by [22][23][24][25][26]. Various nonstandard interactions of neutrinos with matter have been considered [27][28][29][30][31] in particular we mention those by Esteban-Pretel, Tomàs, and Valle [32] looking at the modification of the MSW effect in supernovae [33][34][35], and then again by Blennow, Mirizzi and Serpico [36] and Esteban-Pretel, Tomàs, and Valle [37] where the neutrino-neutrino interactions were included. These studies showed the effect of NSI is to introduce new contributions to the matter potential seen by the neutrinos with strengths (relative to the standard neutrino oscillation contribution to the potential) parameterized by a set of matrices.…”

Alcohol abuse and glycoconjugate metabolism

“…Tuma et al [11] have suggested that acetaldehyde can form adducts with the sulfhydryl groups of tubulin, the contractile protein necessary for secretion process. Diminished secretion could also be due to alcohol-induced alteration in glycoconjugate receptor, as a result of a decrease in its mRNA [45].…”

“…Pre-Golgi transport (from endoplasmic reticulum to Golgi) may be affected by long-term alcohol exposure due to lowered exposure of regulators and effectors of GTPases (e.g. Rab, Rac) [45]. Different studies have described ethanol-induced impairments in exocytosis, endocytosis and nucleocytoplasmic transport that are involved in intracellular traffic of glycoconjugates [45,46].…”

“…Rab, Rac) [45]. Different studies have described ethanol-induced impairments in exocytosis, endocytosis and nucleocytoplasmic transport that are involved in intracellular traffic of glycoconjugates [45,46]. Generally, two trafficking pathways are affected: transport of newly synthesized secretory or membrane glycoproteins from Golgi to the basolateral membrane, and clathrin-mediated endocytosis from the cell surface [46].…”