Abstract
By catalyzing the hydrolysis of sphingomyelin into ceramide, acid sphingomyelinase (ASM) changes the local composition of the plasma membrane with effects on receptor-mediated signaling. Altered enzyme activities have been noted in common human diseases, including alcohol dependence. However, the underlying mechanisms remain largely unresolved. Blood samples were collected from early-abstinent alcohol-dependent in-patients (n[♂] = 113, n[♀] = 87) and matched healthy controls (n[♂] = 133, n[♀] = 107), and analyzed for routine blood parameters and serum ASM activity. We confirmed increased secretory ASM activities in alcohol-dependent patients compared to healthy control subjects, which decreased slightly during detoxification. ASM activity correlated positively with blood alcohol concentration, withdrawal severity, biomarkers of alcohol dependence (liver enzyme activities of gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase; homocysteine, carbohydrate-deficient transferrin; mean corpuscular volume, and creatine kinase). ASM activity correlated negatively with leukocyte and thrombocyte counts. ASM and gamma-glutamyl transferase were also associated in healthy subjects. Most effects were similar for males and females with different strengths. We describe previously unreported associations between ASM activity and markers of liver damage and myelosuppression. Further research should investigate whether this relationship is causal, or whether these parameters are part of a common pathway in order to gain insights into underlying mechanisms and develop clinical applications.
Highlights
Nearly 2.5 million deaths worldwide are attributable to alcohol use, in addition to other consequences of alcohol-related diseases and injuries (World Health Organization: Global status report on alcohol and health)
Disturbances in sphingolipid metabolism have been identified in human studies and animal models of psychiatric disorders [5], including major and mild depression [6,7,8], which share a high comorbidity with alcohol dependence
We replicated our previous observation of increased S-acid sphingomyelinase (ASM) activity in male and female alcohol-dependent patients by examining a large cohort
Summary
Nearly 2.5 million deaths worldwide are attributable to alcohol use, in addition to other consequences of alcohol-related diseases and injuries (World Health Organization: Global status report on alcohol and health). Disturbances in sphingolipid metabolism have been identified in human studies and animal models of psychiatric disorders [5], including major and mild depression [6,7,8], which share a high comorbidity with alcohol dependence. Sphingolipids play an increasingly recognized role in neuronal function in the brain, by serving as a membrane component to form a physical barrier. They influence the local composition of the plasma membrane, the localization and activity of proteins and, receptor-mediated signaling, in addition to their own actions as ligands [9]. De novo biosynthesis and the salvage pathway, lead to the generation of ceramide
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
