Functional implications of novel human acid sphingomyelinase splice variants

Journal article


Publication Details

Author(s): Rhein C, Tripal P, Seebahn A, Konrad A, Kramer M, Nagel C, Kemper J, Bode J, Mühle C, Gulbins E, Reichel M, Becker CM, Kornhuber J
Journal: PLoS ONE
Publication year: 2012
Volume: 7
Journal issue: 4
Pages range: e35467
ISSN: 1932-6203


Abstract


Acid sphingomyelinase (ASM) hydrolyses sphingomyelin and generates the lipid messenger ceramide, which mediates a variety of stress-related cellular processes. The pathological effects of dysregulated ASM activity are evident in several human diseases and indicate an important functional role for ASM regulation. We investigated alternative splicing as a possible mechanism for regulating cellular ASM activity.We identified three novel ASM splice variants in human cells, termed ASM-5, -6 and -7, which lack portions of the catalytic- and/or carboxy-terminal domains in comparison to full-length ASM-1. Differential expression patterns in primary blood cells indicated that ASM splicing might be subject to regulatory processes. The newly identified ASM splice variants were catalytically inactive in biochemical in vitro assays, but they decreased the relative cellular ceramide content in overexpression studies and exerted a dominant-negative effect on ASM activity in physiological cell models.These findings indicate that alternative splicing of ASM is of functional significance for the cellular stress response, possibly representing a mechanism for maintaining constant levels of cellular ASM enzyme activity.



FAU Authors / FAU Editors

Becker, Cord-Michael Prof. Dr.
Medizinische Fakultät
Bode, Jens
Lehrstuhl für Psychiatrie und Psychotherapie
Kornhuber, Johannes Prof. Dr. med.
Lehrstuhl für Psychiatrie und Psychotherapie
Mühle, Christiane Dr. rer. nat.
Psychiatrische und Psychotherapeutische Klinik
Nagel, Christine
Lehrstuhl für Psychiatrie und Psychotherapie
Reichel, Martin PD Dr.
Psychiatrische und Psychotherapeutische Klinik
Seebahn, Angela
Lehrstuhl für Biochemie und Molekulare Medizin
Tripal, Philipp Dr.
Chirurgische Klinik


External institutions with authors

Universität Duisburg-Essen (UDE)
Universitätsklinikum Jena


How to cite

APA:
Rhein, C., Tripal, P., Seebahn, A., Konrad, A., Kramer, M., Nagel, C.,... Kornhuber, J. (2012). Functional implications of novel human acid sphingomyelinase splice variants. PLoS ONE, 7(4), e35467. https://dx.doi.org/10.1371/journal.pone.0035467

MLA:
Rhein, Cosima, et al. "Functional implications of novel human acid sphingomyelinase splice variants." PLoS ONE 7.4 (2012): e35467.

BibTeX: 

Last updated on 2018-10-10 at 02:27