Mechanisms of homocysteic acid neurotoxicity

Arzumanyan, E. S.; Stepanova, M. S.

doi:10.1134/s1819712410030104

Cited by 3 publications

(3 citation statements)

References 13 publications

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“…Of these MAPKs, the best characterized ones are the p38, ERK1/2 (p44/42 MAPK) and JNK serine/threonine kinases that regulate cell survival and cell death [ 49 ]. Kefalogianni and Gaitanaki [ 50 ] previously demonstrated that exogenous H 2 O 2 activates the p38, ERK1/2 (p44/42 MAPK) and JNK signaling pathways in murine C2 myoblasts and, carnosine was found to prevent the activation of ERK1/2 in rats neurons subjected to H 2 O 2 -induced oxidative stress [ 51 ]. Carnosine was also able to reduce the activation of p38 and ERK1/2 MAPKs in rat mesangial cells exposed to high glucose oxidative stress [ 52 ].…”

Section: Resultsmentioning

confidence: 99%

Characterisation of intracellular molecular mechanisms modulated by carnosine in porcine myoblasts under basal and oxidative stress conditions

et al. 2020

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Carnosine is a naturally occurring histidine-containing dipeptide present at high concentration in mammalian skeletal muscles. Carnosine was shown to affect muscle contraction, prevent the accumulation of oxidative metabolism by-products and act as an intracellular proton buffer maintaining the muscle acid-base balance. The present study was undertaken to gain additional knowledge about the intracellular mechanisms activated by carnosine in porcine myoblast cells under basal and oxidative stress conditions. Satellite cells were isolated from the skeletal muscles of 3 to 4 day-old piglets to study the effect of 0, 10, 25 and 50 mM carnosine pre-treatments in cells that were exposed (0.3 mM H 2 O 2) or not to an H 2 O 2-induced oxidative stress. Study results demonstrated that carnosine acts differently in myoblasts under oxidative stress and in basal conditions, the only exception being with the reduction of reactive oxygen species and protein carbonyls observed in both experimental conditions with carnosine pre-treatment. In oxidative stress conditions, carnosine pre-treatment increased the mRNA abundance of the nuclear factor, erythroid 2 like 2 (NEF2L2) transcription factor and several of its downstream genes known to reduce H 2 O 2. Carnosine prevented the H 2 O 2-mediated activation of p38 MAPK in oxidative stress conditions, whereas it triggered the activation of mTOR under basal conditions. Current results support the protective effect of carnosine against oxidative damage in porcine myoblast cells, an effect that would be mediated through the p38 MAPK intracellular signaling pathway. The activation of the mTOR signaling pathway under basal condition also suggest a role for carnosine in myoblasts proliferation, growth and survival.

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Section: Resultsmentioning

confidence: 99%

Characterisation of intracellular molecular mechanisms modulated by carnosine in porcine myoblasts under basal and oxidative stress conditions

et al. 2020

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“…El trastorno cognitivo en homocistinuria, como el que presenta el paciente, se debería a la actividad neurotóxica con aumento de S-adenosilhomocisteína, ácido homocisteíco y ácido sulfínico de la homocisteína, debido al influjo de calcio promovido por la activación de receptores de glutamato tipo NMDA (17). Aquellos pacientes con homocistinuria que mantienen los valores adecuados de homocisteína (<11 μmol/L) desde temprana edad, antes de los 5 años, se relacionan con coeficientes intelectuales normales (18).…”

Section: Discussionunclassified

Homocistinuria, una enfermedad metabólica de diagnóstico tardío en el Perú.

Cornejo‐Olivas¹,

Chávez-Pasco²,

Inca‐Martinez³

et al. 2015

Rev Neuropsiquiatr

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RESUMENLa Homocistinuria, es un desorden metabólico autosómico recesivo, cuya forma clásica es causada por deficiencia de cistationina β-sintasa, debido a mutaciones en el gen CBS (Cr 21q22.3). Se describe el caso de un varón de 17 años con hipopigmentación de piel y faneras, retraso psicomotor moderado, hábito marfanoide, miopía severa, subluxación del cristalino bilateral, que además presentó eventos psicóticos y una hemiparesia izquierda secundaria a un infarto lacunar. La determinación de homocisteína en plasma se encontró elevada (>9,9mg/dl), así como niveles altos de nitroprusiato de sodio en orina(4+) que confirmaron el diagnóstico clínico de homocistinuria. La homocistinuria clásica genera múltiples complicaciones a nivel dérmico, oftalmológico, cognitivo, osteoarticular y psiquiátrico; que podrían evitarse con un diagnóstico y tratamiento oportuno a través del tamizaje neonatal, aún no disponible en la mayoría de centros asistenciales en el Perú.PALABRAS CLAVE: Enfermedades metabólicas, hábito marfanoide, homocistinuria, Perú, diagnóstico tardío. SUMMARYHomocystinuria is an autosomal-recessive metabolic disorder whose classical phenotype is caused by a deficiency of cystathionine β-synthase, due to mutations within the CBS gene (Cr21q22.3). Herein we report a 17 year old man with hypopigmented skin and hair, mental retardation, marfanoid habitus, severe myopia, bilateral lens subluxation, psychotic episodes, and left-sided hemiparesis secondary to a lacunar brain infarction. Laboratory tests showed increased levels of homocysteine (>9.9mg/dl) in plasma and high levels of urinary sodium nitroprusside (4+), consistent with the clinical diagnosis of classical homocystinuria. This systemic disorder includes dermal, ophthalmic, cognitive, osteoarticular and psychiatric alterations, all of which could be potentially prevented with early diagnosis and therapy as part of newborn screening, which is still unavailable in Peru.

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“…HCA локализуется в глиальных клетках префронтальной коры, гипоталамуса, а ее выход из астроцитов имеет место при стимулировании как ионотропных, так и метаботропных глутаматных рецепторов [9]. Многие исследователи отмечают, что токсическое действие Hcy и HCA направлено на глутаматные рецепторы NMDA-типа на нейронах, что приводит к проникновению в нейроны Ca 2+ , вызывая накопление свободных радикалов [8, [10][11][12]. Активные формы кислорода реагируют с ненасыщенными жирными кислотами мембранных липидов и запускают реакции перекисного окисления.…”

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Changes in the concentration of sulfur-containing amino acids in the brain after methionine load in the experimentChanges in the concentration of sulfur-containing amino acids in the brain after methionine load in the experiment

Новогродская

Дорошенко

Курбат

2020

Vescì Nac. akad. navuk Belarusì, Ser. med. navuk

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The effect of methionine overload on the state of the pool of sulfur-containing amino acids and their metabolites was studied in the various brain structures determined by reverse phase high performance liquid chromatography (HPLC). In all regions of the brain studied, methionine led to a unidirectional imbalance of sulfur-containing compounds: there was an increase in the concentrations of methionine, cystathionine and hypotaurine. The most pronounced increase in methionine and hypotaurine levels was observed in the striatum, cystathionine in the hemispheres. A significant increase in taurine concentration was observed only in the hypothalamus and striatum. In other parts of the brain a tendency to increase its level was shown. In all brain regions studied except the striatum, serine levels were decreased. In the cerebellum, in comparison with other regions, an increase in the level of cysteic acid and a decrease in the level of cysteinesulfinic acid were observed, which indicates that taurine synthesis is occurred mainly through the cysteine sulfinate oxidation.

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Mechanisms of homocysteic acid neurotoxicity

Cited by 3 publications

References 13 publications

Characterisation of intracellular molecular mechanisms modulated by carnosine in porcine myoblasts under basal and oxidative stress conditions

Characterisation of intracellular molecular mechanisms modulated by carnosine in porcine myoblasts under basal and oxidative stress conditions

Homocistinuria, una enfermedad metabólica de diagnóstico tardío en el Perú.

Changes in the concentration of sulfur-containing amino acids in the brain after methionine load in the experimentChanges in the concentration of sulfur-containing amino acids in the brain after methionine load in the experiment

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