Bone Marrow Transplantation Reveals the in Vivo Expression of the Mitochondrial Uncoupling Protein 2 in Immune and Nonimmune Cells during Inflammation

Marie-Clotilde Alves-Guerra,Sophie Rousset,Claire Pecqueur,Ziad Mallat,Julie Blanc,Alain Tedgui,Fredéric Bouillaud,Anne-Marie Cassard-Doulcier,Daniel Ricquier,Bruno Miroux

doi:10.1074/jbc.m306951200

Abstract

The mitochondrial uncoupling protein 2 (UCP2) is expressed in spleen, lung, intestine, white adipose tissue, and immune cells. Bone marrow transplantation in mice was used to assess the contribution of immune cells to the expression of UCP2 in basal condition and during inflammation. Immune cells accounted for the total amount of UCP2 expression in the spleen, one-third of its expression in the lung, and did not participate in its expression in the intestine. LPS injection stimulated UCP2 expression in lung, spleen, and intestine in both immune and non-immune cells. Successive injections of LPS and dexamethasone or N-acetyl-cysteine prevented the induction of UCP2 in all three tissues, suggesting that oxygen free radical generation plays a role in UCP2 regulation. Finally, both previous studies and our data show that there is down-regulation of UCP2 in immune cells during their activation in the early stages of the LPS response followed by an up-regulation in UCP2 during the later stages to protect all cells against oxidative stress.

Highlights

UCP21 belongs to a newly discovered subgroup of mitochondrial carrier proteins related to the well known UCP1 from brown adipose tissue
uncoupling protein 2 (UCP2) levels in the lung and duodenum were increased 2.8- and 2.3-fold, respectively, at an LPS concentration of 10 mg/kg; these levels of expression were consistently less than those seen in the spleen (Fig. 1B), which is the predominant organ of UCP2 expression in the conditions examined
The protein band detected below UCP2 is still present in liver mitochondria from Ucp2Ϫ/Ϫ (Fig. 2B, lane 4) and is, not UCP2

Summary

Introduction

UCP21 belongs to a newly discovered subgroup of mitochondrial carrier proteins related to the well known UCP1 from brown adipose tissue (for review, see Ref. 1). LDL RϪ/Ϫ mice, which are susceptible to atherosclerosis when fed an atherogenic diet, were transplanted with bone marrow cells from either Ucp2Ϫ/Ϫ or Ucp2ϩ/ϩ littermate mice In this mouse model of atherosclerosis, the lack of UCP2 accelerated the development of unstable atherosclerotic plaques, showing a protective role for UCP2 in atherosclerosis [5]. The uncoupling activity of all UCPs has been established in vitro in proteoliposomes [13,14,15] and yeast or mammalian mitochondria [16, 17], the in vivo activity of UCP2 and UCP3 is still a matter of debate Another approach to understanding the physiological roles of UCP2 has been to study the expression of the protein in wildtype mice. We investigated the effects of N-acetyl-cysteine and dexamethasone on the expression of UCP2 in the LPS model

Methods

Results

Conclusion