Adaptation Of CPS1 To Hibernation In Bats

Mammalian hibernation, a series of subtle regulated and well organized physiological, morphological, and behavioral changes, is performed by a wide range of species. To survive the cold weather and reduction of energy supply, hibernators reduce body temperature, metabolic rate, and greatly suppress many physiological activities. The main energy source that hibernator use in winter shifts from carbohydrate to fat which is hugely reserved by hyperphagia during late summer. It is observed that body weight of hibernators is mainly lost by burning of preserved fat, but whether protein catabolism accounts for a considerable proportion of body weight loss is unknown. Little loss of proteins is occurred during winter in large hibernators such as bears, while small hibernators such as ground squirrels and bats show an overall protein loss, and the preservation of pectoral muscles and liver proteins is observed.Our previous study has shown that the expression of enzymes involved in amino acid degradation and nitrogen metabolism was significantly elevated in hibernating bats. We investigated the expression and function of CPS1 and OTC in Myotis ricketti bats at their torpor and arousal states, by which the nitrogen metabolism during bat hibernation was explored. Proteins that interact with CPS1 were also investigated by co-immunoprecipitation. CPS1 is the rate limiting enzyme of urea production and represents the activity of nitrogen metabolism of the organism. We further applied Western blotting, enzyme activity assay, and mass spectrometry to study the regulatory mechanisms of CPS1 during bat hibernation.Agmatinase is an important enzyme in the pathway for polyamine biosynthesis and converts agmatine into putrescine. The pathway was first discovered in bacteria, plants, and other lower species. Recent study suggested that it is also functional in mammals as an alternative pathway for polyamine biosynthesis. Agmatinase is correlated with nitrogen metabolism and has close relationship to the urea production but is not directly participate in it. In this study, we found the in vitro evidence that CPS1 has strong interaction with AGMAT. Barely no research have ever found the relationship between agmatinase and urea cycle. The immunoprecipitation, immunofluorescence, and FRET were used to investigate the specific interaction between CPS1 and AGMAT in different mammalian species and the potential adaptive mechanism of the interaction to bat hibernation.