Oxidative stress and aging: Is methylglyoxal the hidden enemy?This review is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.

Abstract

Aging is a multifactorial process that involves changes at the cellular, tissue, organ and the whole body levels resulting in decreased functioning, development of diseases, and ultimately death. Oxidative stress is believed to be a very important factor in causing aging and age-related diseases. Oxidative stress is caused by an imbalance between oxidants such as reactive oxygen species (ROS) and antioxidants. ROS are produced from the mitochondrial electron transport chain and many oxidative reactions. Methylglyoxal (MG) is a highly reactive dicarbonyl metabolite formed during glucose, protein and fatty acid metabolism. MG levels are elevated in hyperglycemia and other conditions. An excess of MG formation can increase ROS production and cause oxidative stress. MG reacts with proteins, DNA and other biomolecules, and is a major precursor of advanced glycation end products (AGEs). AGEs are also associated with the aging process and age-related diseases such as cardiovascular complications of diabetes, neurodegenerative diseases and connective tissue disorders. AGEs also increase oxidative stress. In this review we discuss the potential role of MG in the aging process through increasing oxidative stress besides causing AGEs formation. Specific and effective scavengers and crosslink breakers of MG and AGEs are being developed and can become potential treatments to slow the aging process and prevent many diseases.

Long-Term Methylglyoxal Treatment Causes Endothelial Dysfunction of Rat Isolated Mesenteric Artery

“…75(2): 151-157, 2013 Methylglyoxal (MGO) is an alpha-dicarbonyl compound that is spontaneously formed in a process of glycolysis from dihydroxyacetone phosphate as a by-product during a formation of glyceraldehyde 3-phosphates in most mammalian cells including vascular endothelial cells [20] and smooth muscle cells [25]. In addition, MGO is formed in some enzymatic processes by the enzymes including MGO synthase, cytochrome P450 2E1 and semicarbazide-sensitive amine oxidase [4]. MGO binds to arginine, cysteine and lysine residues in proteins, which causes a non-enzymatic formation of a number of advanced glycation end-products (AGEs) [28] including argpyrimidine [19] and N ε -(carboxyethyl) lysine [1].…”

Aldehydes participation in oxidative stress in rat thymocytes in vitro

“…The ability of MGL to induce oxidative stress [15] was demonstrated by Desai, Chang et al on the different types of cells. These results indicate that aldehydes, are formed on the crossing of different metabolic ways, are very important for research of these processes.…”

“…Glycation is a complex series of parallel and sequential reactions, in which reducing free carbonyl groups of carbohydrates react with the nucleophilic amino groups of biomolecules, producing a large number of various aldehydes. Reactive aldehydes formed during these ways are, for example, saturated aldehydes (ethanal [1], propanal), non-saturated ones (acrolein (ACR) [2], 4-hydroxynonenal [3]) and dicarbonyls (glyoxal (GL), methylglyoxal (MGL) [4] Aldehydes can alkylate amino groups of amino acids and basics of nucleic acids; react with proteins and peptides with further creation of stable intermediate products such as Schiff bases or N-hydroxymethyl adducts. In addition, these carbonyl compounds are able to form methylene bridges between close parts in proteins, that causes defection in their activity [5,6].…”

The influence of natural dicarbonils on the antioxidant enzymes activity in vitro and in vivo

“…осуществляться двумя способами: путём гликирования -прямого присоединения молекулы глюкозы при взаимодействии свободных аминогрупп протеинов с альдегидной группой этого углевода, либо путём реакции аминогрупп белков с дикарбонилами, образующимися вследствие процесса глиоксилирования -автоокисления глюкозы или фрагментации триозофосфатов [10,11]. Отмеченное многими авторами резкое накопление a-оксоальдегидов, в частности глиоксаля и метилглиоксаля, в крови больных при диабете [12][13][14][15][16][17][18][19][20] приводит к развитию карбонильного стресса [10,11].…”

“…Отмеченное многими авторами резкое накопление a-оксоальдегидов, в частности глиоксаля и метилглиоксаля, в крови больных при диабете [12][13][14][15][16][17][18][19][20] приводит к развитию карбонильного стресса [10,11]. Нами установлено, что при реакции метилглиоксаля с аминогруппами концевых аминокислот белков, подобных апоВ-100 ЛНП, может происходить генерирование супероксидных анион-радикалов [21], что должно сопровождаться интенсификацией свободнорадикальных реакций, включая автоокисление глюкозы.…”