Ethanol alters access to the cell nucleus

Abstract

Ethanol is the most frequently used drug among humans. We tested the hypothesis whether ethanol, at clinically relevant concentrations modifies, signaling across the nuclear envelope (NE). In cell nuclei isolated from Xenopus oocytes, we measured NE electrical resistance and NE macromolecule permeability 1 to 20 h after addition of ethanol (0.05 to 0.2%). Furthermore, with atomic force microscopy, nuclear pores of the NE were imaged after exposure to ethanol. We found that NE permeability decreased within hours of ethanol exposure. In parallel, nuclei swell and nuclear pores form clusters in the NE. Force measurements on individual nuclear pores indicate that pores found in clusters are stiffer than those found randomly distributed in the NE. Application of a transcription blocker (actinomycin D) or RNase treatment of isolated nuclei in vitro after ethanol exposure prevents the permeability changes. In conclusion, ethanol, at commonly used concentrations, changes NE structure by transcriptional processes in the cell nucleus. Within hours, the NE becomes less permeable for diffusible ions and macromolecules. This could explain altered signaling to and communication with the cell nucleus in the pathophysiology of alcohol abuse.

Exceptional mechanical and structural stability of HSV-1 unveiled with fluid atomic force microscopy

“…The measured value of HSV-1 capsid stiffness seems to further support this hypothesis. However, the stiffness of the capsid in question is enormously high compared with the stiffness values of cellular structures known to interact with incoming virions, such as the plasma membrane (Hoh and Schoenenberger, 1994) and the nuclear pores (Schafer et al, 2007), which are below 10 pN/nm (Oberleithner, 2005). Moreover, the fairly high stiffness value of HSV-1 capsids raises the question as to how these structures are 'cracked' for the release of the enclosed viral genome upon binding to nuclear pores.…”

“…AFM produces three-dimensional images of biological surfaces at molecular scale (Engel and Muller, 2000) in a physiologically relevant environment (Del Sol et al, 2007;Greenleaf et al, 2007). Beyond this one-of-a-kind capability, AFM can also be applied to biological samples for a variety of key mechanical investigations, such as volume and stiffness measurements at the nano-scale (Hillebrand et al, 2006;Schafer et al, 2007). It is therefore unsurprising that AFM qualifies as a suitable technique for uncovering physiologically relevant alterations of viral structural assemblies by modelling corresponding steps of the viral life cycle in vitro (Kuznetsov et al, 2003).…”

Imaging CFTR in its native environment

“…Atomic force microscopy (AFM), however, allows high-resolution imaging under physiological conditions. This allows the study of functional changes in structure as shown, e.g., for nuclear pores [17,68,69,81,91] and endothelial cells [66,87].…”

Human Tyrosyl-DNA Phosphodiesterase 1 Possesses Transphosphooligonucleotidation Activity With Primary Alcohols

“…At the cell nucleus level, ethanol is able to alter access to the cell nucleus by changing the nuclear envelope structure, a double-layered lipid bilayer, penetrated by nuclear pore complexes, thus, the nuclear envelope becomes less permeable for diffusible ions and macromolecules. This could explain altered signaling to and communication with the cell nucleus in the pathophysiology of alcohol abuse (Schäfer et al, 2007). A large body of evidence has shown that alcohol and especially chronic alcohol use can have epigenetic effects, namely, site-selective acetylation, methylation, and phosphorylation in histone, nucleosomal remodeling via histone modifications and DNA methylation (Shukla et al, 2008;Tulisiak et al, 2017;Ciafrè et al, 2019).…”