Repessé Xavier, Moldes Marthe, Muscat Adeline, Vatier Camille, Chetrite Gérard, Gille Thomas, Planes Carole, Filip Anna, Mercier Nathalie, Duranteau Jacques, Fève Bruno
UMR S_1185, INSERM, Université Paris-Sud, Le Kremlin-Bicêtre, France; Service de Réanimation Médico-Chirurgicale, pôle Thorax-Vaisseaux-Abdomen-Métabolisme, Hôpital Ambroise Paré, Assistance Publique-Hôpitaux de Paris, Boulogne-Billancourt, France.
Centre de Recherche Saint-Antoine, INSERM, UMR S_938, Sorbonne Universités, Université Paris 6, Paris, France; Institut Hospitalo-Universitaire ICAN, Paris, France.
Mol Cell Endocrinol. 2015 Aug 15;411:58-66. doi: 10.1016/j.mce.2015.04.011. Epub 2015 Apr 20.
Semicarbazide-sensitive amine oxidase (SSAO), an enzyme highly expressed on adipocyte plasma membranes, converts primary amines into aldehydes, ammonium and hydrogen peroxide, and is likely involved in endothelial damage during the course of diabetes and obesity. We investigated whether in vitro, adipocyte SSAO was modulated under hypoxic conditions that is present in adipose tissue from obese or intensive care unit. Physical or pharmacological hypoxia decreased SSAO activity in murine adipocytes and human adipose tissue explants, while enzyme expression was preserved. This effect was time-, dose-dependent and reversible. This down-regulation was confirmed in vivo in subcutaneous adipose tissue from a rat model of hypoxia. Hypoxia-induced suppression in SSAO activity was independent of the HIF-1-α pathway or of oxidative stress, but was partially antagonized by medium acidification. Hypoxia-induced down-regulation of SSAO activity could represent an adaptive mechanism to lower toxic molecules production, and may thus protect from tissue injury during these harmful conditions.
氨基脲敏感胺氧化酶(SSAO)是一种在脂肪细胞质膜上高度表达的酶,可将伯胺转化为醛、铵和过氧化氢,可能参与糖尿病和肥胖症病程中的内皮损伤。我们研究了在肥胖或重症监护病房的脂肪组织中存在的缺氧条件下,体外脂肪细胞SSAO是否受到调节。物理性或药物性缺氧可降低小鼠脂肪细胞和人脂肪组织外植体中的SSAO活性,而酶表达得以保留。这种效应具有时间和剂量依赖性且是可逆的。在缺氧大鼠模型的皮下脂肪组织中,体内实验证实了这种下调作用。缺氧诱导的SSAO活性抑制与HIF-1-α途径或氧化应激无关,但部分受到培养基酸化的拮抗。缺氧诱导的SSAO活性下调可能是一种降低有毒分子产生的适应性机制,因此可能在这些有害条件下保护组织免受损伤。