Characterization of a Neutral Sphingomyelinase Activity in Human Serum and Plasma

Mühle, Christiane; Kornhuber, Johannes

doi:10.3390/ijms24032467

Cited by 3 publications

(2 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It could be informative to extend activity assays to further enzymes of the sphingolipid pathway such as acid and neutral ceramidases and sphingomyelinases. Recent evidence suggests the latter to be detectable in human serum/plasma samples [ 73 ]. Neutral sphingomyelinase was also found to be strongly reduced in the hippocampus of PD-induced mice in association with neuroinflammation [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

Peripheral Upregulation of Parkinson’s Disease-Associated Genes Encoding α-Synuclein, β-Glucocerebrosidase, and Ceramide Glucosyltransferase in Major Depression

Brazdis,

von Zimmermann,

Lenz

et al. 2024

IJMS

Self Cite

View full text Add to dashboard Cite

Due to the high comorbidity of Parkinson’s disease (PD) with major depressive disorder (MDD) and the involvement of sphingolipids in both conditions, we investigated the peripheral expression levels of three primarily PD-associated genes: α-synuclein (SNCA), lysosomal enzyme β-glucocerebrosidase (GBA1), and UDP-glucose ceramide glucosyltransferase (UGCG) in a sex-balanced MDD cohort. Normalized gene expression was determined by quantitative PCR in patients suffering from MDD (unmedicated n = 63, medicated n = 66) and controls (remitted MDD n = 39, healthy subjects n = 61). We observed that expression levels of SNCA (p = 0.036), GBA1 (p = 0.014), and UGCG (p = 0.0002) were higher in currently depressed patients compared to controls and remitted patients, and expression of GBA1 and UGCG decreased in medicated patients during three weeks of therapy. Additionally, in subgroups, expression was positively correlated with the severity of depression and anxiety. Furthermore, we identified correlations between the gene expression levels and PD-related laboratory parameters. Our findings suggest that SNCA, GBA1, and UGCG analysis could be instrumental in the search for biomarkers of MDD and in understanding the overlapping pathological mechanisms underlying neuro-psychiatric diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Peripheral Upregulation of Parkinson’s Disease-Associated Genes Encoding α-Synuclein, β-Glucocerebrosidase, and Ceramide Glucosyltransferase in Major Depression

Brazdis,

von Zimmermann,

Lenz

et al. 2024

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…The blood samples will be analyzed by measuring the concentration of biomarkers such as growth and immune factors using commercial antibody-based and other detection methods. The activities of enzymes involved in sphingolipid metabolism will be determined via established assays using fluorescently labeled substrates [55,56]. Peripheral blood mononuclear cells are isolated by Ficoll gradient centrifugation and stored at −150 • C for subsequent immunophenotyping.…”

Section: Blood Collection and Analysis And Hrvmentioning

confidence: 99%

TaKeTiNa Music Therapy for Outpatient Treatment of Depression: Study Protocol for a Randomized Clinical Trial

Behzad,

Feldmann-Schulz,

Lenz

et al. 2024

JCM

Self Cite

View full text Add to dashboard Cite

Background/Objectives: Depression is a prevalent and debilitating illness that significantly affects psychological and physical well-being. Apart from conventional therapies such as psychotherapy and medication, individuals with depression often lack opportunities for activities that are generally perceived as enjoyable, such as music, meditation, and arts, which have demonstrated therapeutic effectiveness. TaKeTiNa music therapy has been employed as a therapeutic intervention for more than two decades. However, there is a notable absence of well-designed clinical trials investigating its antidepressant effects, a gap we aim to address in our current study. Furthermore, shifts in the progression of depression may manifest both psychologically, by influencing emotional states, and physiologically, by leading to alterations in lipid and sphingolipid metabolism, cortisol levels, and immune system function. Our study seeks to analyze the impact of TaKeTiNa music therapy on both levels. Methods: This is a prospective monocentric randomized waitlist-controlled clinical trial. It investigates the influence of TaKeTiNa music therapy on patients with major depression in an outpatient setting. Therefore, interested persons are randomly assigned to two groups, an intervention group or a control group, after completing a screening procedure. The intervention group starts with an eight-week TaKeTiNa music therapy intervention. The waiting group receives the same therapy program after completing the follow-up period. Blood and saliva sampling as well as responses to questionnaires are obtained at specific time points. Discussion: Our study investigates the effects of TaKeTiNa music therapy, a non-pharmacological antidepressant treatment option, on depressive symptoms. We also address functional and causal immunological changes; hormonal changes, such as changes in cortisol levels; and metabolic changes, such as changes in serum lipids and sphingolipids, during the course of depression. We expect that this study will provide evidence to expand the range of treatment options available for depression.

show abstract

Inhibition of the HV1 voltage-gated proton channel compromises the viability of human polarized macrophages in a polarization- and ceramide-dependent manner

Kovacs,

Cs. Szabo,

Kothalawala

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

The human voltage-gated proton channel (HV1) provides an efficient proton extrusion pathway from the cytoplasm contributing to the intracellular pH regulation and the oxidative burst. Although its pharmacological inhibition was previously shown to induce cell death in various cell types, no such effects have been examined in polarized macrophages albeit HV1 was suggested to play important roles in these cells. This study highlights that 5-chloro-2-guanidinobenzimidazole (ClGBI), the most widely applied HV1 inhibitor, reduces the viability of human THP-1-derived polarized macrophages at biologically relevant doses with M1 macrophages being the most, and M2 cells the least sensitive to this compound. ClGBI may exert this effect principally by blocking HV1 since the sensitivity of polarized macrophages correlates well with their HV1 expression levels; inhibitors of other macrophage ion channels that may be susceptible for off-target ClGBI effects cause no viability reductions; and Zn2+, another non-specific HV1 blocker, exerts similar effects. As a potential mechanism behind the ClGBI-induced cell death, we identify a complex pH dysregulation involving acidification of the cytoplasm and alkalinization of the lysosomes, which eventually result in membrane ceramide accumulation. Furthermore, ClGBI effects are alleviated by ARC39, a selective acid sphingomyelinase inhibitor supporting the unequivocal significance of ceramide accumulation in the process. Altogether, our results suggest that HV1 inhibition leads to cellular toxicity in polarized macrophages in a polarization-dependent manner, which occurs due to a pH dysregulation and concomitant ceramide overproduction mainly depending on the activity of acid sphingomyelinase. The reduced macrophage viability and plausible concomitant changes in homeostatic M1-M2 balance could contribute to both the therapeutic and potential side effects of HV1 inhibitors that show great promise in the treatment of neuroinflammation and malignant diseases.

show abstract

Characterization of a Neutral Sphingomyelinase Activity in Human Serum and Plasma

Cited by 3 publications

References 54 publications

Peripheral Upregulation of Parkinson’s Disease-Associated Genes Encoding α-Synuclein, β-Glucocerebrosidase, and Ceramide Glucosyltransferase in Major Depression

Peripheral Upregulation of Parkinson’s Disease-Associated Genes Encoding α-Synuclein, β-Glucocerebrosidase, and Ceramide Glucosyltransferase in Major Depression

TaKeTiNa Music Therapy for Outpatient Treatment of Depression: Study Protocol for a Randomized Clinical Trial

Inhibition of the HV1 voltage-gated proton channel compromises the viability of human polarized macrophages in a polarization- and ceramide-dependent manner

Contact Info

Product

Resources

About