Active Turnover of Heme in Hibernation Period in Mammals.

Hong Pyo Kim,Hee Min Yoo,Namki Cho,Phil Jun Lee

doi:10.3389/fphys.2019.01586

Abstract

Heme oxygenase (HO)-1 plays an important role during hibernation by catalyzing the degradation of heme to biliverdin/bilirubin, ferrous iron, and carbon monoxide, which activates the protective mechanisms against stress. In this context, it was important to analyze the metabolic processes of heme. Nevertheless, to date, no study has approached on biosynthesis of heme. Therefore, our study aims to understand the process of heme biosynthesis, which regulates cell survival in conditions of hypothermia and calorie restriction (CR). During hibernation, the mRNA levels of enzymes responsible for de novo heme biosynthesis were increased in the liver tissue of a Syrian hamster model of hibernation. Moreover, heme trafficking and iron metabolism were found to be more active, as assessed based on the changes in the levels of heme transporter and ferroportin mRNA. The levels of HO-1, a powerful antioxidant, were also upregulated during hibernation. Additionally, increased levels of Sirt-1 mRNA were also observed. These enzymes are known to act as cellular metabolic sensors that activate the cytoprotective mechanisms. These results indicate that HO-1 induction, brought about by the upregulation of heme during the pre-hibernation period, may protect against external stress. Here, we describe heme catabolism during hibernation by analyzing the regulation of the key molecular players involved in heme metabolism. Therefore, this study offers a new strategy for the better regulation of intracellular heme concentrations during hypothermia and other stresses.

Highlights

Certain mammals, including primates undergo hibernation, a state in which the animals become inactive (Dausmann et al, 2004)
Upregulation of the aminolevulinic acid synthase (ALAS), uroporphyrinogen decarboxylase (UROD), coproporphyrinogen oxidase (CPOX), and FECH mRNAs was consistently observed during pre-hibernation (Figure 1B)
We assessed the levels of heme biosynthetic enzymes in animals under the conditions of starvation and pre-hibernation, as pre-hibernation routinely consists of both hypothermia and starvation

Summary

Introduction

Certain mammals, including primates undergo hibernation, a state in which the animals become inactive (Dausmann et al, 2004). In small rodents, such as the Syrian golden hamster, Mesocricetus auratus, hibernation has two phases: torpor and arousal. The core temperature of the animals and the metabolic rate return back to normal (normal body temperature, 37◦C) (Körtner and Geiser, 2000). The profound metabolic depression of torpor reduces energetically expensive cellular processes, such as transcription and translation, and physiological functions, such as heart rate, respiration, Heme Biosynthesis in Pre-hibernation immune and renal function, and neural activity (Carey et al, 2003). Hibernators avoid cellular and tissue injury when metabolic demand is reduced

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