Redox Functions of Heme Oxygenase-1 and Biliverdin Reductase in Diabetes. (February 2018)

• Record Type: Journal Article
• Authors: Rochette, Luc; Zeller, Marianne; Cottin, Yves; Vergely, Catherine
• Is Part Of: Trends in endocrinology and metabolism. Volume 29:Number 2(2018)
• Page Start: 74
• Page End: 85
• Publication Date: 2018-02
• Subjects: diabetes -- oxidative stress -- reactive oxygen species -- inflammation -- heme oxygenase-1 -- biliverdin reductase; Endocrinology -- Periodicals; Metabolism -- Periodicals; Metabolism; 616.4
• DOI: 10.1016/j.tem.2017.11.005
• Languages: English
• ISSNs: 1043-2760

Abstract

Abstract : In patients with diabetes, the hyperglycemia-driven excess generation of reactive oxygen species (ROS) induces oxidative stress (OS) in a variety of tissues. OS is closely associated with chronic inflammation and has a key role in the pathogenesis of vascular complications. The enzymes that generate ROS and gasotransmitters are redox regulated and are implicated in cellular signaling. As a result of cellular metabolism, cells produce significant amounts of carbon monoxide (CO), mainly from heme degradation catalyzed by heme oxygenases (HOs). These reactions also generate biliverdin, bilirubin (BR), and iron. The conversion of biliverdin to BR is catalyzed by biliverdin reductase-A (BVR-A). In this review, we focus on the importance of the HO-1/CO system and BVR in the pathophysiology and therapy of inflammation associated with diabetes. Highlights: Heme proteins have a major role in various biological functions and most of the reactions involving heme are redox reactions of heme iron. Heme is released from hemoproteins during red blood cell destruction and is metabolized by HOs (two isoforms: HO-1 and HO-2). These generate signaling molecules through the catalysis of heme (CO, biliverdin, BR, and iron). The conversion of biliverdin to BR is catalyzed by BVRs. HOs and BVRs are closely involved in cellular adaptation to OS and the inflammatory response associated with various cardiometabolic diseases, such as diabetes. Recent studies suggest a trigger role for HO-1 in insulin resistance. The diversity of the protective effects of HO-1 inducers has led to major interest in their therapeutic use. A variety of drugs have been studied in experimental protocols but the challenge is to translate these into clinical practice. Therapeutic strategies with more-specific modulators of inflammatory pathways may become a more-engaging approach in the future.