Protein Pyrrole Adducts in Diabetes Mellitus

Chen, Xiao; Jiang, Zhuyi; Spencer, Peter S.

doi:10.1007/978-3-031-08014-2_52

Xiao Chen⁵,
Zhuyi Jiang⁶ &
Peter S. Spencer⁷

Part of the book series: Biomarkers in Disease: Methods, Discoveries and Applications ((BDMDA))

1052 Accesses

Abstract

Diabetes mellitus is commonly associated with a symmetrical, distal sensory or sensorimotor axonal polyneuropathy that develops insidiously and advances in accord with the hyperglycemic state. Elevated blood glucose promotes anaerobic glycolysis which in turn produces excess advanced glycation end products, many of which have a pyrrole structure that can react with critical neuroproteins. Pyrroles also form between endogenous γ-diketones, notably 2,5-hexanedione, and the ε-amine group of lysine residues of proteins, including those required for axonal maintenance. The pyrrolated proteins undergo oxidation and cross-linkage, which interferes with axonal transport of materials from sites of neuronal synthesis to distal destinations. Thus, the distal ends of elongate sensory and motor axons are first affected, which triggers distal nerve fiber degeneration. Comparable pathological changes in long tracts of the spinal cord result in an overall picture of central-peripheral distal axonopathy. Whether, which, and what levels of pyrrolated serum/urinary proteins are useful biological markers of diabetic polyneuropathy is the principal subject of this chapter.

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Abbreviations

AA:: Acetoacetate
ACHD:: 3-Acetyl-2,5-hexanedione
AFGP:: Alkyl formylglycosyl pyrrole
AGE:: Advanced glycation end product
CNS:: Central nervous system
COVID-19:: SARS-CoV-2-induced disease
CPDA:: Central-peripheral distal axonopathy
DEHD:: 3,4-Diethyl-2,5-hexanedione
DiPHD:: 3,4-Diisopropyl-2,5-hexanedione
DM:: Diabetes mellitus
DM-1:: DM type 1
DM-2:: DM type 2
DMAB:: p-Dimethylaminobenzaldehyde
DMHD:: 3,4-Dimethyl-2,5-hexanedione
DPP-4:: Dipeptidyl peptidase 4
DSPN:: Distal sensory/sensorimotor peripheral neuropathy
GDM:: Gestational DM
HbA1c:: Hemoglobin A1c
3-HHD:: 3-Hydroxy-2,5-hexanedione
4-HNE:: 4-Hydroxy-2-nonenal
HO-1:: Heme oxygenase 1
ICAM-1:: Intercellular adhesion molecule 1
IL-1:: Interleukin 1
IL-6:: Interleukin 6
IL-1RA:: Interleukin 1 receptor antagonist
MALAT1:: Metastasis-associated lung adenocarcinoma transcript 1
MCP-1:: Monocyte chemoattractant protein 1
MG :: Methylglyoxal
miRNA:: Microribonucleic acid
NADPH:: Nicotinamide adenine dinucleotide phosphate
NFE2L2:: Nuclear factor, erythroid 2-like 2
NF-κB:: Nuclear factor-κB
NMR:: Nuclear magnetic resonance
PARP-α:: Poly[ADP-ribose]polymerase 1
PNS:: Peripheral nervous system
RAGE:: Receptor for AGE
SARS-CoV-2:: Severe acute respiratory syndrome coronavirus 2
SDS-PAGE:: Sodium dodecyl sulfate polyacrylamide gel electrophoresis
sICAM-1:: Soluble intercellular adhesion molecule 1
SIRT1:: Sirtuin 1
TGF-β:: Transforming growth factor beta
TNF-α:: Tumor necrosis factor alpha
TRPV1:: Transient receptor potential cation channel subfamily V member 1
VEGF:: Vascular endothelial growth factor

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Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Medical Key Subject of Health Toxicology, (2020–2024), Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China
Xiao Chen
Department of Endocrinology, Shenzhen People’s Hospital, Shenzhen, Guangdong, China
Zhuyi Jiang
Department of Neurology, School of Medicine and Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, OR, USA
Peter S. Spencer

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School of Life Sciences, University of Westminster, London, UK
Vinood B. Patel
Department of Nutrition and Dietetics, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, UK
Victor R. Preedy

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Chen, X., Jiang, Z., Spencer, P.S. (2023). Protein Pyrrole Adducts in Diabetes Mellitus. In: Patel, V.B., Preedy, V.R. (eds) Biomarkers in Diabetes. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Cham. https://doi.org/10.1007/978-3-031-08014-2_52

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