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[Effects of polyamine-loaded liposomes on liver mitochondrial permeability transition]
M Costuleanu1, Liliana Foia, Natalia Costuleanu
1Facultatea de Medicină Stomatologică, Universitatea de Medicină şi Farmacie Gr.T. Popa Iaşi.
Abstract:
The objective of the present study was represented by the effects of polyamineloaded liposomes on hepatic mitochondrial permeability transition (MPT). MPT was appreciated through the swelling of the isolated guinea-pig liver mithocondria induced by Ca2+, at 540 nm, using a diode-array 8452 UV-VIS spectrophotometer and a General Purpose software (Hewlett-Packard). Polyamines encapsulated in liposomes might inhibit the appearance of MPT induced by Ca2+, directly proportional to electrical charge: spermine > spermidine > putrescine > cadaverine. Thus, together with some previous data, it was observed that spermine may modulate hepatic MPT from the exterior, as well as from the interior of mitochondria. Moreover, spermidine and putrescine may also modulate MPT from the interior of mitochondria at low doses, and from the exterior only at high doses. The changes in mitochondrial membranes lipid composition (as done by control liposomes) are slightly influencing the MPT. The increase in membrane rigidity through the use of 40% cholesterol-enriched liposomes is drastically decreasing the appearance and development of MPT.
Insights
Polyamine-loaded liposomes inhibit hepatic mitochondrial permeability transition (MPT). The inhibition effect is charge-dependent, with spermine showing the strongest effect, modulating MPT from both inside and outside mitochondria.
Area of Science:
- Biochemistry
- Cell Biology
- Mitochondrial research
Context:
- Hepatic mitochondrial permeability transition (MPT) is a critical process in cell death.
- Liposomes are widely used for drug delivery and modulating cellular processes.
- Understanding MPT modulation is crucial for developing therapeutic strategies.
Purpose:
- To investigate the effects of polyamine-loaded liposomes on hepatic mitochondrial permeability transition (MPT).
- To determine the relationship between polyamine charge and their ability to inhibit Ca2+-induced MPT.
- To explore the influence of liposomal membrane composition on MPT.
Summary:
- Polyamine-loaded liposomes were studied for their effects on isolated guinea-pig liver mitochondria undergoing Ca2+-induced MPT.
- MPT inhibition by polyamines in liposomes was directly proportional to their electrical charge: spermine > spermidine > putrescine > cadaverine.
- Spermine modulated MPT from both mitochondrial interior and exterior, while spermidine and putrescine showed dose-dependent modulation.
- Cholesterol-enriched liposomes significantly reduced MPT, indicating membrane rigidity influences the process.
Impact:
- Polyamines encapsulated in liposomes can modulate hepatic MPT, offering potential therapeutic applications.
- Liposomal composition, particularly membrane rigidity, plays a significant role in controlling MPT.
- This study provides insights into the mechanisms of MPT regulation by liposomes and polyamines.