Related Experiment Videos
[Biologic effect of LDL binding and intracellular degradation in monocytes from patients with hypercholesterolemia]
G Fóris1, E Kovács, M Szabolcs
1Debreceni Orvostudományi Egyetem, Központi Kutató Laboratórium.
Insights
Monocytes from hypercholesterolemia patients show reduced inositol phosphate levels, indicating impaired post-receptor signaling. This suggests a defect in signal transmission, not LDL receptor number, in these patients.
Area of Science:
- Immunology
- Metabolic Disorders
Background:
- Previous studies indicated reduced post-receptor signaling in granulocytes from elderly patients.
- Monocytes from patients with non-insulin-dependent diabetes mellitus (NIDDM) showed decreased LDL degradation and cholesterol synthesis.
- It was hypothesized that NIDDM patients with hypercholesterolemia have normal monocyte LDL receptor numbers but damaged post-receptor signal transmission.
Purpose of the Study:
- To investigate the post-receptor signal mechanism in monocytes from hypercholesterolemia patients.
- To compare signaling pathways before and after LDL treatment in patient and control groups.
- To assess the impact of LDL and FMLP stimulation on monocyte signaling.
Main Methods:
- Monocytes were isolated from 12 hypercholesterolemia patients and 11 age-matched healthy controls.
- Cells were treated with LDL and stimulated with chemotactic peptide FMLP.
- Inositol phosphate (IP) levels, intracellular calcium (Ca2+) elevation, and protein tyrosine (PT) resistance were measured.
Main Results:
- Inositol phosphate levels decreased in the hypercholesterolemia patient group, irrespective of the stimulus.
- LDL-induced elevation of IP3 and Ca2+ levels was observed in both patient and control groups.
- This LDL-induced signaling pathway was found to be protein tyrosine (PT) resistant in both groups.
Conclusions:
- Monocytes from hypercholesterolemia patients exhibit impaired inositol phosphate production.
- The findings support the hypothesis of damaged post-receptor signal transmission in hypercholesterolemia.
- Further research is needed to elucidate the specific molecular mechanisms underlying this signaling defect.
Abstract:
The granulocytes from elderly patients were investigated, in previous studies, with FMLP and it was found that the postreceptor signal, the inositol phosphate production and inositol phosphate dependent calcium signal were markedly reduced. It was observed that the 125I LDL binding was slightly reduced while the intracellular degradation of the LDL and endogenous cholesterol synthesis inhibitory effect was significantly decreased on monocytes of patients with non insulin dependent diabetes mellitus. It was suggested that of in patients suffering from NIDDM with hypercholesterolemia the LDL receptor numbers of monocytes are close to normal, while the post receptor signal transmission is damaged. In this study the monocytes from 12 patients with hypercholesterolemia were investigated before and after LDL treatment and were compared to the 11 age-matched healthy volunteer control patients. The cells were stimulated with LDL and chemotactic peptide FMLP. The postreceptor signal mechanism in monocytes was investigated. According to the results the inositol phosphate level of the patient group decreased independently from the stimulus. The LDL induced IP3 and Ca2+ level elevation was PT resistant both in the control and in the patients group.