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Abstract
The output of the master clock to control peripheral circadian functions and temporal organization in metazoans is unknown. We recently reported a periodic dip of lipidperoxidation (PDL) at 03 h in humans by monitoring the serum levels of malondialdehyde (MDA), a marker of lipidperoxidation, over a 24-hour period and suggested that PDL may represent a redox signal of the master clock. Mitochondria are considered to be the major source of lipidperoxidation in most tissues. Their activity is known to be disrupted in many malignant tissues. To test the possible role of mitochondrial activity on the induction of the PDL, we monitored the daily MDA levels in the serum of 16 cancer patients, suffering from different kinds of malignant tumors, and compared them with those found in the healthy humans of our previous study. Discriminant analysis revealed a significant difference between both groups only at 03 h ( p = 0.000001), thus indicating the critical relevance of this time point for differences between both groups. In the light of the emerging role of the mitochondrion in cell signaling, we suggest that the signal transduction from the master clock may be related to central and peripheral mitochondrial activity and its ROS (reactive oxygen species) generation. This notion could involve nitric oxide, as a known potent regulator of mitochondrial function and as an essential part of the mitochondrial signaling pathway. The PDL could additionally be useful as a circadian phase marker in chronobiology research.
Acknowledgments
I am deeply indebted to all the test persons who took part in this examination. I thank Dr. rer. nat. Wolfgang Bayer, the head of Laboratorium Dr. Bayer, Stuttgart, for his generous support and for implementing the MDA measurements. I also thank Dave Miller for his valuable comments and Dr. Wolfgang Reimers, who performed the statistic analyses.