Correction of Age-Related Disorders of Sphingolipid Content in Rat Tissues by Acid Sphingomyelinase Inhibition

Gar’kavenko, V. V.; Storozhenko, G. V.; Krasnikova, Olga N.; Babenko, N. A.

doi:10.1615/intjphyspathophys.v3.i3.80

Cited by 4 publications

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“…of aged animals: by 197%, 168% and 164%, respectively, as compared to 3-month old animals. Thus, taking together these results and data obtained previously (Babenko and Shakhova 2006;Sacket et al 2009;Garkavenko et al 2012) it is evident that at old age SMase activity increases in the rat tissues.…”

Section: Age-related Changes Of Sphingolipids Contentsupporting

confidence: 84%

“…At the same time, zoledronic acid chronic administration has been reported not to influence on body weight gain in rats, but in humans it can lead to either weight increase or weight loss (Khajuria et al 2015). Our previous works showed that optimal administration period for imipramine to inhibit effectively ASMase activity in 24-month old rats was 14 days (Garkavenko et al 2012). Effective period of zoledronic acid administration is known to be about 10 days (Yamashita et al 2011).…”

Section: Imipramine and Zoledronic Acid Effects On The Body And Organmentioning

confidence: 99%

“…These results clearly demonstrated the impact of multiple pathways of SL turnover on ceramide accumulation in the hepatocytes at old age. In contrast, in such brain structures, as hippocampus and neocortex, imipramine increased the SM level (Garkavenko et al 2012), but did not change the ceramide content (Babenko and Shakhova 2014a). However, inhibition of neutral SMase by means of N-acetylcysteine or calorie-restricted diet nullified the age-induced ceramide accumulation in the brain (Babenko and Shakhova 2014a) and improved cognitive function of old rats (Babenko and Shakhova 2014b).…”

Section: Introductionmentioning

confidence: 99%

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Role of acid sphingomyelinase in the age-dependent dysregulation of sphingolipids turnover in the tissues of rats

Babenko

Gar’kavenko²,

Storozhenko³

et al. 2016

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Old age-associated pathologies usually coincide with altered sphingolipid metabolism. In the present article, the role of acid sphingomyelinase (ASMase) in the age-dependent changes of sphingomyelin (SM) and ceramide contents in the tissues has been investigated by means of ASMase inhibitors, imipramine and zoledronic acid. It has been determined that ceramide content and ceramide/SM ratio increased, while SM level decreased in the heart, liver, blood serum and skeletal muscles of 24-month old rats in contrast to 3-month old animals. Injections of imipramine or zoledronic acid to 24-month old rats resulted in significant downregulation of ASMase in the liver and skeletal and heart muscles. The both inhibitors decreased the ceramide content and ceramide/SM ratio and increased the SM content in all tissues studied, except the heart, of old rats to the levels close to those observed in the young animals. Long-term treatment of rats by inhibitors, which have different mechanisms of action on ASMase, exerts the similar, but not equal effects on enzyme activity and SM turnover. In summary, the data above strongly suggest that the age-dependent up-regulation of ASMase plays an important role in the modulation of ceramide and SM contents in rat tissues and that imipramine and zoledronic acid are useful tools for SM turnover manipulation at old age.

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Section: Age-related Changes Of Sphingolipids Contentsupporting

confidence: 84%

Section: Imipramine and Zoledronic Acid Effects On The Body And Organmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Role of acid sphingomyelinase in the age-dependent dysregulation of sphingolipids turnover in the tissues of rats

Babenko

Gar’kavenko²,

Storozhenko³

et al. 2016

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“…В пользу данного предположения свидетельствуют установленное нами повышение соотношения церамид/СФМ в ДРП крыс 24-месячного возраста (на 224 % в сравнении с молодыми животными) (рис., В), а также результаты исследований, проведенных на различных органах и тканях и показавших существенную активацию кСФМазы в процессе старения [11,16]. Высказано предположение, что кСФМазе принадлежит важная роль в развитии ассоциированного с возрастом нарушения баланса СФЛ.…”

Section: результаты и их обсуждениеunclassified

“…R. W. Jenkins и соавторы [10] на клетках MCF7 продемонстрировали дозозависимое подавление активности кСФМазы имипрамином в экспериментах как in vivo, так и in vitro. Установлено также, что длительное введение старым 24-месячным крысам мелипрамина сопровождается существенным повышением в печени, сердце, неокортексе и гиппокампе содержания СФМ и снижением соотношения церамид/СФМ по сравнению с контрольными животными [11]. Учитывая вышесказанное, можно предположить возможность коррекции при помощи данного препарата возрастных нарушений обмена СФЛ, а также улучшения рецепции и реализации инсулиновых сигналов в скелетной мускулатуре.…”

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The Role of Acid Sphingomyelinase in Insulin-Induced Glucose Uptake Violations by Muscle Tissue in Old Age

Babenko

Timoﬁychuk

2013

PEP

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It was study the possibility of correction of violations of the insulin-induced glucose uptake bymuscle tissue of older rats by inhibiting acid sphingomyelinase (aSMase) with imipramine. Foundthat in muscle tissue 24-month-old rats, there are an accumulation of ceramide, weight sphingomyelin(SM) and the growth of the ratio of ceramide/SM compared to 3-month-old rats. The introductionof imipramine old animal, like the introduction of the drug in the incubation medium of the extensordigitorum longus, induces a decrease in the level of ceramide accumulation of SM and drops of theratio of ceramide/SM compared with the control, which may be due to the ability of the drug toinhibit the activity of aSMase. Eﬀect of imipramine in vitro accompanied by improved insulin-inducedglucose uptake by muscle tissue of old rats. It is suggested that aSMase does an important role in themodulation of insulin signaling in target tissues in old age through the production of ceramide.

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Changes in the Sphingolipid Content in Tissues and Behavioral Modifications of Rats Subjected to Neurogenic Stress: Role of Sphingomyelinases

2016

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Correction of Age-Related Disorders of Sphingolipid Content in Rat Tissues by Acid Sphingomyelinase Inhibition

Cited by 4 publications

References 0 publications

Role of acid sphingomyelinase in the age-dependent dysregulation of sphingolipids turnover in the tissues of rats

Role of acid sphingomyelinase in the age-dependent dysregulation of sphingolipids turnover in the tissues of rats

The Role of Acid Sphingomyelinase in Insulin-Induced Glucose Uptake Violations by Muscle Tissue in Old Age

Changes in the Sphingolipid Content in Tissues and Behavioral Modifications of Rats Subjected to Neurogenic Stress: Role of Sphingomyelinases

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