Full Description
Mammalian heme peroxidase enzymes play a critical role in innate immune responses and disease prevention. The formation of potent chemical oxidants is essential to this protective physiologic activity in immunity. Although highly beneficial in the context of immune defense, it is now well established that peroxidases and their overproduction of oxidants contribute to the initiation and persistence of many chronic inflammatory conditions in the cardiovascular, neurologic, respiratory, renal, and gastrointestinal systems. Peroxidasins, a protein family related to heme peroxidases, play a novel role in tissue biogenesis and matrix assembly, which are also attracting attention in different pathological contexts. Given the diverse roles of mammalian heme peroxidases and the breadth and incidence of pathologies associated with these enzymes, there has been significant interest in modulating peroxidase activity as a therapeutic strategy. This book highlights recent developments in our understanding of the chemistry, biochemistry and biological roles of mammalian peroxidases and their associated oxidants, their involvement in both innate immunity and chronic inflammatory disease in a variety of end organs, and potential therapeutic approaches to modulate and prevent damaging reactions.
Key Features
Structure and biosynthesis of mammalian peroxidases
Reactivity of hypohalous acids with biological substrates
Peroxidases in innate immunity
Peroxidases in human pathology
Modulation of peroxidase-induced biological damage
Contents
SECTION 1: INTRODUCTION TO MAMMALIAN HEME PEROXIDASES
Structure, function, phylogeny of heme peroxidases
Biosynthesis of MPO and other heme peroxidases
Peroxidasin structure and function
SECTION 2: REACTIVITY OF PEROXIDASE OXIDANTS
Reactivity of peroxidase oxidants with proteins and proteoglycans
Reactivity of peroxidase with nucleic acids, RNA and DNA
Reactivity of peroxidase oxidants with lipids - modification and signaling
Role of MPO in the modification of lipoproteins (LDL and HDL)
Regulation of cellular signaling and survival by peroxidase oxidants
Global profiling of cell responses to peroxidase oxidants
SECTION 3: PEROXIDASES IN INNATE IMMUNITY
MPO and immune cell recruitment and activation
Role of MPO in extracellular trap release by neutrophils
Imaging HOCl production by neutrophils
How microbes combat reactive chlorine species
Priming the innate immune system to combat respiratory disease
SECTION 4: PEROXIDASES IN PATHOLOGY
Imaging the reactivity of MPO in vivo
Role of MPO in vascular dysfunction and signaling
MPO in ischemic heart disease
Role of MPO in neurodegenerative disease
Role of MPO in kidney disease
Role of peroxidases in respiratory disease
Role of peroxidasins in disease
SECTION 5: PREVENTION OF MPO INDUCED DAMAGE
Design and functionality of MPO inhibitors
Modulation of disease using MPO inhibitors
Novel peroxidase inhibitory protein "SPIN" with broad target specificity
Selenium and resistance to oxidative enzyme inactivation
