Hibernation impact on the catalytic activities of the mitochondrial D-3-hydroxybutyrate dehydrogenase in liver and brain tissues of jerboa (Jaculus orientalis)

Abstract

BackgroundJerboa (Jaculus orientalis) is a deep hibernating rodent native to subdesert highlands. During hibernation, a high level of ketone bodies i.e. acetoacetate (AcAc) and D-3-hydroxybutyrate (BOH) are produced in liver, which are used in brain as energetic fuel. These compounds are bioconverted by mitochondrial D-3-hydroxybutyrate dehydrogenase (BDH) E.C. 1.1.1.30. Here we report, the function and the expression of BDH in terms of catalytic activities, kinetic parameters, levels of protein and mRNA in both tissues i.e brain and liver, in relation to the hibernating process.ResultsWe found that: 1/ In euthemic jerboa the specific activity in liver is 2.4- and 6.4- fold higher than in brain, respectively for AcAc reduction and for BOH oxidation. The same differences were found in the hibernation state. 2/ In euthermic jerboa, the Michaelis constants, KM BOH and KM NAD+ are different in liver and in brain while KM AcAc, KM NADH and the dissociation constants, KD NAD+and KD NADH are similar. 3/ During prehibernating state, as compared to euthermic state, the liver BDH activity is reduced by half, while kinetic constants are strongly increased except KD NAD+. 4/ During hibernating state, BDH activity is significantly enhanced, moreover, kinetic constants (KM and KD) are strongly modified as compared to the euthermic state; i.e. KD NAD+ in liver and KM AcAc in brain decrease 5 and 3 times respectively, while KD NADH in brain strongly increases up to 5.6 fold. 5/ Both protein content and mRNA level of BDH remain unchanged during the cold adaptation process.ConclusionsThese results cumulatively explained and are consistent with the existence of two BDH enzymatic forms in the liver and the brain. The apoenzyme would be subjected to differential conformational folding depending on the hibernation state. This regulation could be a result of either post-translational modifications and/or a modification of the mitochondrial membrane state, taking into account that BDH activity is phospholipid-dependent.

Differential Regulation of Peroxisome Proliferator-Activated Receptor (PPAR)-α1 and Truncated PPARα2 as an Adaptive Response to Fasting in the Control of Hepatic Peroxisomal Fatty Acid β-Oxidation in the Hibernating Mammal

“…Our previous studies have shown that prehibernation of jerboas is associated with hypotriglyceridemia and hypoketonemia, which result from a high rate of fatty acid and triacylglycerol uptake concomitant with depressed mitochondrial and peroxisomal fatty acid oxidation in adipose tissues (27,28). We have also reported the participation of jerboa PPAR isotypes b/d and g in brown fat non-shivering thermogenesis and in white fat adipogenesis during hibernation bouts, respectively (28).…”

Possible Role of Extracellular Vesicles in Hepatotoxicity of Acetaminophen

“…The loss of important enzymes in EVs shed by APAP-treated rat livers, which are involved in the metabolism of xenobiotics, such as cytochromes P450, cytochrome b5, and cytochrome b5 reductase, is an indication of severe oxidative stress [ 103 ]. Furthermore, the loss of UGT enzymes that play a key role in the elimination of xenobiotics is also an additional sign of severe cellular stress [ 20 , 25 , 26 , 27 , 28 , 29 ].…”