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Role of pinoline and melatonin in stabilizing hepatic microsomal membranes against oxidative stress
J J García1, R J Reiter, J Pié
1Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, 78229-3900, USA.
Abstract:
We investigated the influence of pinoline (0.01-1.5 mM) on microsomal membrane fluidity before and after rigidity was induced by oxidative stress. In addition, we tested the effect of pinoline in the presence of 1 mM melatonin. The fluidity in rat hepatic microsomes was monitored using fluorescence spectroscopy and it was compared to the inhibition of malonaldehyde (MDA) plus 4-hydroxyalkenals (4-HDA) production as a reflection of lipid peroxidation. Below 0.6 mM, pinoline inhibited membrane rigidity in a manner parallel to its inhibitory effect on MDA + 4-HDA formation. At concentrations between 1-1.5 mM, pinoline was less effective in stabilizing microsomal membranes than was predicted from its inhibition of lipid peroxidation. The addition of 1 mM melatonin enhanced the membrane-stabilizing activity of pinoline (0.01-0.6 mM). This cooperative effect was not observed for concentrations of pinoline between 1-1.5 mM. When pinoline was tested without induced oxidative damage, 1-1.5 mM pinoline maintained membrane fluidity at the same level as that recorded after induced lipid peroxidation. The results suggest that pinoline may be another pineal molecule that prevents membrane rigidity mediated by lipid peroxidation and this ability is enhanced by melatonin.
Insights
Pinoline helps maintain cell membrane fluidity, preventing rigidity caused by oxidative stress. Melatonin enhances this protective effect at lower pinoline concentrations.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Oxidative stress can induce rigidity in microsomal membranes.
- Lipid peroxidation, measured by malonaldehyde (MDA) and 4-hydroxyalkenals (4-HDA) production, contributes to membrane rigidity.
- The pineal gland produces molecules that may protect against oxidative damage.
Purpose of the Study:
- To investigate the effect of pinoline on microsomal membrane fluidity.
- To determine if pinoline protects against oxidative stress-induced membrane rigidity.
- To examine the combined effect of pinoline and melatonin on membrane fluidity.
Main Methods:
- Rat hepatic microsomes were used to assess membrane fluidity.
- Fluorescence spectroscopy monitored changes in membrane fluidity.
- Lipid peroxidation was quantified by measuring MDA and 4-HDA production.
Main Results:
- Pinoline (0.01-0.6 mM) inhibited membrane rigidity and lipid peroxidation.
- Higher pinoline concentrations (1-1.5 mM) were less effective in stabilizing membranes than predicted by lipid peroxidation inhibition.
- Melatonin (1 mM) enhanced pinoline's membrane-stabilizing effect at lower concentrations (0.01-0.6 mM).
Conclusions:
- Pinoline acts as a pineal molecule that prevents membrane rigidity induced by lipid peroxidation.
- Melatonin enhances the membrane-protective effects of pinoline.
- The interaction between pinoline and melatonin is concentration-dependent.