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Melatonin inhibits oxidative modification of human low‐density lipoprotein
Author(s) -
Kelly Melissa R.,
Loo George
Publication year - 1997
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.1997.tb00323.x
Subject(s) - tbars , melatonin , chemistry , low density lipoprotein , thiobarbituric acid , lipid peroxidation , lipoprotein , oxidative phosphorylation , apolipoprotein b , lysophosphatidylcholine , biochemistry , antioxidant , endocrinology , medicine , phospholipid , cholesterol , phosphatidylcholine , biology , membrane
An important property of melatonin is that it is a free‐radical scavenger or antioxidant. Since free radicals can induce oxidative modification of low‐density lipoprotein (LDL), a process believed to be involved in atherogenesis, we were prompted to evaluate the capacity of melatonin to prevent oxidative modification of LDL. To induce oxidation, human LDL (0.4 mg protein/ml) was incubated at 37°C with either 10 μM cupric chloride or 10 mM 2,2′‐azo‐bis‐(2‐amidinopropane) dihydrochloride (AAPH) for 3 hr or 24 hr, respectively. Several assays were then performed to unequivocally determine the extent of LDL oxidation. Compared to native LDL, oxidized LDL had increased agarose gel electrophoretic mobility and weaker immunoreactivity with a murine monoclonal antibody to human apolipoprotein B‐100. Measurement of thiobarbituric acid‐reactive substances (TBARS) revealed that native LDL contained 1.8 ± 0.6 nmoles TBARS/mg protein, whereas copper‐oxidized LDL contained 53 ± 4 nmoles TBARS/mg protein. However, when present during incubation, melatonin (0.125–4 mM) inhibited in a concentration‐dependent manner the increase in electrophoretic mobility, decrease in immunoreactivity of LDL, and increase in formation of TBARS caused by either copper or AAPH. In a fourth assay, phospholipid analysis of LDL was performed. Native LDL contained 420 ± 9 nmoles phosphatidylcholine (PC)/mg LDL protein and 30 ± 20 nmoles lysophosphatidylcholine (LysPC)/mg LDL protein. LDL incubated with copper had a decreased PC content (276 ± 48 nmoles PC/mg LDL protein) and increased LysPC content (76 ± 22 nmoles LysPC/mg LDL protein). But when present during the incubation of LDL with copper, melatonin attenuated in a concentration‐dependent manner the degradation of PC to LysPC. Therefore, we conclude that melatonin can inhibit oxidative modification of LDL in vitro.