The effect of isatin on protein-protein interactions between cytochrome b5 and cytochromes P450

Ершов, П. В.; Yablokov, E. O.; Mezentsev, Yu. V.; Kalushskiy, L A; Florinskaya, A. V.; Veselovsky, A. V.; Gnedenko, O. V.; Gilep, Andrei A.; Usanov, Sergey A.; Медведев, А. Е.; Иванов, А. С.

doi:10.18097/pbmc20176302170

Cited by 13 publications

(8 citation statements)

References 26 publications

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“…This strengthens a recently proposed role of isatin as a regulator of PPIs in living organisms. Taken together with previous data on decreased affinity of some PPIs in the presence of isatin these results indicate that isatin can exhibit multidirectional effects on PPIs: an increase in affinity of one type of PPIs and a decrease in affinity of other type of PPIs. At the same time, insensitivity of some pairs of PPIs investigated in this study to isatin also indicates that the regulatory effects of isatin on PPI are rather specific and do not cover all possible PPIs.…”

Section: Resultssupporting

confidence: 85%

“…We have hypothesized that in addition to direct action on particular protein targets, isatin can act as a regulator of protein–protein interactions (PPIs). Indeed, results of our recent studies suggest that isatin can decrease affinity of some PPI . In this study we performed an surface plasmon resonance (SPR)‐based biosensor analysis for PPIs, which would demonstrate altered affinity in the presence of isatin.…”

Section: Introductionmentioning

confidence: 99%

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Isatin‐induced increase in the affinity of human ferrochelatase and adrenodoxin reductase interaction

et al. 2017

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Isatin (indol-2,3-dione) is an endogenous non-peptide regulator exhibiting a wide range of biological and pharmacological activities, which are poorly characterized in terms of their molecular mechanisms. Identification of many isatin-binding proteins in the mammalian brain and liver suggests that isatin may influence their functions. We have hypothesized that besides direct action on particular protein targets, isatin can act as a regulator of protein-protein interactions (PPIs). In this surface plasmon resonance-based biosensor study we have found that physiologically relevant concentrations of isatin (25-100 μM) increase affinity of interactions between human recombinant ferrochelatase (FECH) and NADPH-dependent adrenodoxin reductase (ADR). In the presence of increasing concentrations of isatin the Kd values demonstrated a significant (up to 6-fold) decrease. It is especially important that the interaction of isatin with each individual protein (FECH, ADR) was basically negligible and therefore could not contribute to the observed effect. This effect was specific only for the FECH/ADR complex formation and was not observed for other protein complexes studied: FECH/cytochrome b5(CYB5A) and FECH/SMAD4.

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Section: Resultssupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Isatin‐induced increase in the affinity of human ferrochelatase and adrenodoxin reductase interaction

et al. 2017

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“…Для подавляющего большинства идентифицированных изатин-связывающих белков (особенно ферментов) функциональное значение взаимодействия с изатином остается неясным. С учётом появляющихся данных о влиянии изатина на различные белок-белковые взаимодействия [16][17][18], различия в профиле изатин-связывающих белков мозга и печени могут свидетельствовать об участии идентифицированных белков в различных (суб)интерактомах. Нельзя исключить также, что обнаруженные различия в профиле изатин-связывающих белков, по-видимому, играют важную роль в специфических эффектах изатина в определённых органах.…”

Section: материалы и методыunclassified

Comparative proteomic analysis of mouse liver and brain isatin-binding proteins

Buneeva

Kopylov

Згода

et al. 2018

BMCRM

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Isatin (indol-2,3-dione) is an endogenous indole, exhibiting various biological activities that are realized via its interacts with numerous target proteins (so-called isatin-binding proteins). To date, isatin-binding proteins have been characterized in the brain of mice and rats. In this study we have performed a comparative proteomic analysis of the isatin-binding proteins of the mouse liver and brain. Proteomic profiling of clarified lysates of membrane and soluble fractions of liver and brain homogenates was performed using 5-aminocaproyl-isatin as an affinity ligand. During affinity based separation of isatin-binding proteins of soluble and membrane fractions of mouse brain homogenates lysed with Triton X-100, 63 individual proteins were identified. A similar separation of mouse liver homogenate fractions during affinity chromatography resulted in identification of 80 proteins. All identified liver and brain proteins belonged to the following functional groups: (I) Carbohydrate metabolism and energy generation; (II) Lipid metabolism; (III) Metabolism of nucleotides and amino acids; (IV) Formation of the cytoskeleton, exocytosis; (V) Regulation of gene expression, cell division and differentiation; (VI) Antioxidant and protective proteins; (VII) Signal transmission and regulation of enzyme activity. The total number of isatin-binding proteins common for the brain and liver was only 12. The most common for the brain and liver of isatin-binding proteins was found in group VI (antioxidant and protective proteins), complete absence of coincidence in group II (lipid metabolism) and group IV (formation of the cytoskeleton, exocytosis). The observed differences in the profile of isatin-binding proteins appear to play an important role in the specific effects of isatin in certain organs.

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“…Для подавляющего большинства идентифицированных изатин-связывающих белков (особенно ферментов) функциональное значение взаимодействия с изатином остается неясным. С учётом данных о влиянии изатина на различные белок-белковые взаимодействия [21][22][23] есть все основания полагать, что изменение профиля изатин-связывающих белков в динамике МФТП-индуцированного паркинсонизма отражает изменения интерактома, вызванные как введением нейротоксина, так и последующими (по-видимому, компенсаторными?) процессами в клетках.…”

Section: протеомныеunclassified

The effect of neurotoxin MPTP administration to mice on the proteomic profile of brain isatin-binding proteins

et al. 2017

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Isatin (indole-2,3-dione) is an endogenous indole found in the mammalian brain, peripheral organs and body fluids. It acts as a neuroprotector, which decreases manifestation of locomotor impairments in animal models of Parkinson's disease. A wide range of biological activity of isatin is associated with interaction of this regulator with numerous isatin-binding proteins. The aim of this study was to investigate the profile of brain isatin-binding proteins in mice with MPTP-induced Parkinsonism (90 min and seven days after administration of this neurotoxin). A single dose administration of MPTP (30 mg/kg, ip.) was accompanied by locomotor impairments in the open field test 90 min after administration; seven days after MPTP administration locomotor activity of mice significantly improved but did not reach the control level. Five independent experiments on proteomic profiling of isatin-binding proteins resulted in confident identification of 96±12 proteins. Development of MPTP-induced locomotor impairments was accompanied by a significant decrease in the number of isatin-binding proteins (63±6; n=5; p<0.01). Seven days after MPTP administration the total number of identified proteins increased and reached the control level (132±34; n=4). The profiles of isatin-binding proteins were rather specific for each group of mice: in the control group these proteins (which were not found in both groups of MPTP-treated mice) represented more than 70% of total proteins. In the case of MPTP treated mice this parameter was 60% (90 min after MPTP administration) and >82% (seven days after MPTP administration). The major changes were found in the groups of isatin-binding proteins involved into cytoskeleton formation and exocytosis, regulation of gene expression, cell division and differentiation and also proteins involved in signal transduction.

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The effect of isatin on protein-protein interactions between cytochrome b5 and cytochromes P450

Cited by 13 publications

References 26 publications

Isatin‐induced increase in the affinity of human ferrochelatase and adrenodoxin reductase interaction

Isatin‐induced increase in the affinity of human ferrochelatase and adrenodoxin reductase interaction

Comparative proteomic analysis of mouse liver and brain isatin-binding proteins

The effect of neurotoxin MPTP administration to mice on the proteomic profile of brain isatin-binding proteins

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