Acid Sphingomyelinase Impacts Canonical Transient Receptor Potential Channels 6 (TRPC6) Activity in Primary Neuronal Systems
Abstract
:1. Introduction
2. Materials and Methods
2.1. Rat Neuronal Cell Culture
2.2. ASM Mouse Strain and Murine Cell Culture
2.3. Genotyping of Mice
2.4. Enzymatic Activity Assay
2.5. Lipid Quantification by Liquid Chromatography Tandem-Mass Spectrometry (LC-MS/MS)
2.6. Mouse Neuronal Ca2+ Measurements
2.7. Mouse Synaptosomal Preparations and Synaptosomal Ca2+ Measurements
2.8. Rat Cortical Phospho-CREB Immunocytochemistry
2.9. Mouse Cortical Phospho-CREB Immunocytochemistry
2.10. Animal Welfare Declaration
2.11. Statistical Analyses
3. Results
3.1. ASM Activity Is Decreased in Cortices of ASM KO Mice
3.2. Genetic ASM Deficiency Impacts the Sphingolipidome in the Murine Frontal Cortex
3.3. Genetic ASM Deficiency Decreases Hyperforin-Induced Ca2+ Influx in Primary Murine Neuronal Cells and Synaptosomes
3.4. ASM Activity Inhibition Prevents Hyperforin-Induced CREB Phosphorylation in Primary Rat Neuronal Cells
3.5. Genetic ASM Deficiency Impacts Hyperforin-Induced CREB-Phosphorylation in Primary Murine Neuronal Cells
4. Discussion
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
Abbreviation | Full Name |
Anti/anti | antibiotic/antimycotic |
ARC39 | C10 bisphosphonate 1-aminodecane-1,1-bisphosphonic acid |
ASM | acid sphingomyelinase |
ASM KO | ASM-knockout |
ASM WT | ASM-wildtype |
Cer | ceramide |
CREB | cAMP response element-binding protein |
DAG | diacylglycerol |
DAPI | 4′,6-diamidino-2-phenylindole |
DIV | days in vitro |
DMEM | Dulbecco’s Modified Eagle’s Medium |
DMSO | dimethyl sulfoxide |
E 18 | embryonic day 18 |
EGTA | ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid |
FCS | fetal calf serum |
Fura-2-AM | Fura-2-acetoxymethylester |
GAD2/65 | glutamic acid decarboxylase 2/65 |
gp | guinea pig |
HBSS-/- | Hank’s balanced salt solution without calcium and magnesium |
HBSS+/+ | Hank’s balanced salt solution with calcium and magnesium |
HPLC | high-performance liquid chromatography |
hyp | hyperforin |
MAP 2 | microtubule associated protein 2 |
MDD | major depressive disorder |
MQ | Millipore water |
ms | mouse |
MS | mass spectrometry |
NB | Neurobasal |
NBA | Neurobasal A |
P | postnatal age |
PBS | phosphate buffered saline |
PC12 | pheochromocytoma 12 cell line |
PCR | polymerase chain reaction |
pCREB | phospho-CREB (serine 133) |
PPD-mix | papain-dispase-DNase mixture |
rb | rabbit |
RT | room temperature (20–22 °C) |
S1P | sphingosine 1-phosphate |
SRM | selected reaction monitoring |
SDS | sodium dodecylsulfate |
SM | sphingomyelin |
Sph | sphingosine |
TBST | TRIS buffered saline + 1% (v/v) Tween |
TRIS | tris(hydroxymethyl)-aminomethan |
TRPC6 | canonical transient receptor potential channel 6 |
USA | United States of America |
UV | ultraviolet light |
vs. | versus |
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Zeitler, S.; Schumacher, F.; Monti, J.; Anni, D.; Guhathakurta, D.; Kleuser, B.; Friedland, K.; Fejtová, A.; Kornhuber, J.; Rhein, C. Acid Sphingomyelinase Impacts Canonical Transient Receptor Potential Channels 6 (TRPC6) Activity in Primary Neuronal Systems. Cells 2020, 9, 2502. https://doi.org/10.3390/cells9112502
Zeitler S, Schumacher F, Monti J, Anni D, Guhathakurta D, Kleuser B, Friedland K, Fejtová A, Kornhuber J, Rhein C. Acid Sphingomyelinase Impacts Canonical Transient Receptor Potential Channels 6 (TRPC6) Activity in Primary Neuronal Systems. Cells. 2020; 9(11):2502. https://doi.org/10.3390/cells9112502
Chicago/Turabian StyleZeitler, Stefanie, Fabian Schumacher, Juliana Monti, Daniela Anni, Debarpan Guhathakurta, Burkhard Kleuser, Kristina Friedland, Anna Fejtová, Johannes Kornhuber, and Cosima Rhein. 2020. "Acid Sphingomyelinase Impacts Canonical Transient Receptor Potential Channels 6 (TRPC6) Activity in Primary Neuronal Systems" Cells 9, no. 11: 2502. https://doi.org/10.3390/cells9112502