Projects per year
Abstract
The sphingolipid de novo synthesis pathway, encompassing the sphingolipids, the enzymes and the cell membrane receptors, are being investigated for their role in diseases and as potential therapeutic targets. The intermediate sphingolipids such as dihydrosphingosine (dhSph) and sphingosine (Sph) have not been investigated due to them being thought of as precursors to other more active lipids such as ceramide (Cer) and sphingosine 1 phosphate (S1P). Here we investigated their effects in terms of collagen synthesis in primary rat neonatal cardiac fibroblasts (NCFs). Our results in NCFs showed that both dhSph and Sph did not induce collagen synthesis, whilst dhSph reduced collagen synthesis induced by transforming growth factor β (TGFβ). The mechanisms of these inhibitory effects were associated with the increased activation of the de novo synthesis pathway that led to increased dihydrosphingosine 1 phosphate (dhS1P). Subsequently, through a negative feedback mechanism that may involve substrate-enzyme receptor interactions, S1P receptor 1 expression (S1PR1) was reduced.
Original language | English |
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Article number | 100837 |
Number of pages | 11 |
Journal | IJC Heart & Vasculature |
Volume | 35 |
DOIs | |
Publication status | Published - Aug 2021 |
Keywords
- Cardiac fibroblasts
- Collagen synthesis
- Dihydrosphingosine
- Sphingolipid
- TGFβ
Projects
- 2 Finished
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Novel approaches to the prevention and treatment of chronic heart disease and its co-morbid complications
Reid, C. (Primary Chief Investigator (PCI)), Kelly, D. (Chief Investigator (CI)), Krum, H. (Chief Investigator (CI)), Liew, D. (Chief Investigator (CI)) & Liew, D. (Chief Investigator (CI))
National Health and Medical Research Council (NHMRC) (Australia)
1/01/16 → 31/12/20
Project: Research
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Mechanisms underlying the contribution of uremic toxins to cardiorenal syndrome
Krum, H. (Primary Chief Investigator (PCI)), Kelly, D. (Chief Investigator (CI)), Kompa, A. (Chief Investigator (CI)) & Wang, B. (Chief Investigator (CI))
National Health and Medical Research Council (NHMRC) (Australia)
1/01/15 → 31/12/17
Project: Research