facebook
twitter
vk
instagram
linkedin
google+
tumblr
akademia
youtube
skype
mendeley
Wiki

CHOLINE CONTAINING PHOSPHOLIPIDS AND PRODUCTS OF LIPID PEROXIDATION IN ERYTHROCYTE AND LYMPHOCYTE MEMBRANES AT FAMILIAL MEDITERRANEAN FEVER

Автор Доклада: 
Karageuzyan K.
Награда: 
CHOLINE CONTAINING PHOSPHOLIPIDS AND PRODUCTS OF LIPID PEROXIDATION IN ERYTHROCYTE AND LYMPHOCYTE MEMBRANES AT FAMILIAL MEDITERRANEAN FEVER


CHOLINE CONTAINING PHOSPHOLIPIDS AND PRODUCTS OF LIPID PEROXIDATION IN ERYTHROCYTE AND LYMPHOCYTE MEMBRANES AT FAMILIAL MEDITERRANEAN FEVER

Konstantin Karageuzyan, Prof. academician
The scientific-technological Centre of organic and pharmaceutical chemistry of the Armenian National Academy of Sciences

 

A B S T R A C T

Our data obtained have shown that development of the Familial Mediterranean Fever is accompanied by the specific abnormalities in the different metabolic processes, especially in the metabolism of phospholipids. It is show that remission period and especially the stage of acute fit of this disease are accompanied by the significant disorders in the physiologically established stability of phospholipid-phospholipid interrelation in the different biological systems in the organism, particularly in the erythrocytes and especially in the lymphocytes membranes. The changes mentioned are characterized by the simultaneous activation of the intensity of the free radical processes, which lead to the formation of high concentrations of malonyl dyaldehyde as the final product of the peroxideformation. The deacylation process of phospholipids-glycerides is accompanied by formation of the extremely high quantities of lysophosphatidylcholines, which in contrary to the other representatives of the neutral and acidic phospholipids are not normalized under the action even of the super low concentrations of the sodium tyosulphate (10-6M, 10-9M, 10-12M), which are known as a doses with very high antioxidant activity. This fact was one of the point at issue of the Annual meeting of the New-York Academy of sciences at 2002, have been devoted to the role of the lysolipids and eucosanoids in biology and pathological physiology.

Introduction
The Familial Mediterranean Fever (FMF) is disease which etiopathogenesis still is not clarified. The discovery in this field was the identification of the gene and its product pirine, which function finally is not revealed. However, the presence of FMF gene is not a sufficient symptom of illness, it revealed not at all patients, at the same time known the cases when the disease has no manifestation at the people have this gene.

Although the natural conjecture about infectious FMF etiology was examined, the infectious theory of FMF till now has not found confirmation. However, it is impossible to exclude participation of microorganisms in start of inflammatory process, as known for today pathogenetic processes during FMF directly are connected to key cells of inflammatory response.

The early results of our investigations [1,3,9-11,14] carried out in the Institute of Molecular Biology of NAS RA on studying in nature of stimulating action of ds-RNA analogue (new modification made by the staff) on immune status of organism, have demonstrated a number of new phenomena. They refer the main component of biological membranes of tissue cell formations on various levels of their phylogenesis differentiation, namely phospholipids (PL). Among PL known by their wide spectrum of structural-functional and metabolic properties, the most interesting appeared to be the fraction of lysophosphatidylcholines (LPC), which was noticeable increased in its contents on the background of effects of ds-RNA certain concentrations [12]. The observed fact was interpreted as a specific phenomenon referring to the quantitative increase of LPC mainly that participate in the complex of molecular and biological changes and condition phenomenon of formation, getting stable to the general immune response of the organism, it stable immune status [2,4-8].

To develop those investigations we undertook special observation in the direction of studying the dynamics of quantitative changes of various categories of PL on the level of erythrocyte and lymphocyte membranes (EM, LM) of patients with FMF. An interest to such an approach was raised by unique ethiopathogenesis of that diseased state, which is till now considered as a genetic disease with rather less studied immune properties and specificity of clinical manifestations.

Materials and Methods
Investigations were carried out on EM and LM of blood taken from patients with FMF during acute fit and remission. Obtaining of EM and LM, estimation of qualitative changes of individual Pl and their sum were carried out with known classic methods [13].

Blood (5ml) from 62 patients with FMF from different hospitals in Yerevan, as weal as from 21 unaffected donors was collected from the ulnar vein into citrate or oxalate (9:1, by volume 1,34% solution); isolation of EM, extraction of total lipids and PL from EM wet substances, fractionation of their choline containing individual representatives, determination of thiobarbituric acid reactive material concentrations in biological materials studied were done by us [1,11] according to the well-known methods.

Results and discussion
The results of studies obtained in EM from the patients with FMF by the above mentioned stereotype at remission stage are given in table 1. It let us establish the qualitative and quantitative changes of neutral PL, such as LPC and phosphatidylcholines (PC). The most noteworthy is the 6 fold increase of LPC in EM, which could hardly be compared with other quantitative changes of other PL categories with decreasing and increasing contents.

One of the explanations of this phenomenon can be interpreted as a reflection of the adaptive reaction of the organism directed to the maximal mobilization of its internal potentials to provide necessary level for resistance, which is summed by various biologically justified components including immune factor.

Further processing of those investigations was directed to study the LPC contents dynamics of the same patients at an acute fit (abdominal, thoracic, mixed), to which sound manifestations of the oxidative stress was peculiar.

As it is seen in the same table 1 an acute fit of FMF is characterized by a significant increase in EM of the quantity of LPC, which was more pronounced and it was almost 10 fold over the control.

According to the date of table 1, it is obvious that in LM (in compare with EM) at non-attack remission period more sound increase of LPC is observed, which prevails 8 fold over the one of the healthy persons, while that change at fit is over the initial indices 12 fold.

According to the date of table 2, PD at stage of remission is characterized by significant action of free radical peroxidation (FRP) of lipids in EM especially in ascorbate dependent system of lipid peroxidation. 2h incubation of EM in presence of different concentrations of sodium thyosulfate (10-6, 10-9 and 10-12M of STS) is accompanied by the lowering of malonyl dialdehyde (MDA) quantity in EM especially when 10-12M of STS was used. In this case 2h incubation of EM leads to the complete normalization of MDA content, which not demonstrates the statistically verified difference in compare with control indexes.

Our date obtained have shown that abnormalities mentioned in the intensity of FRP processes in EM at remission period of FMF become more pronounced in LM at the same period of investigation. As one can see in table 2, as in case of EM here also the intensity of FRP process is more accented in ascorbate-dependent system of lipid peroxidation. At the same time it is necessary to note that in LM peroxidation of lipids proceeds more active then in EM and accompanied with the formation of comparative high concentrations of the products of peroxidation.

Another picture was observed in dynamics of MDA in EM at the stage of acute fit on persons with FMF. As it can been seen in table 2, acute period of the disease is characterized by significant elevation of the level of peroxidation products in EM, and the quantity of MDA is not normalized even after 2h incubation of EM in the presence of 10-6 and 10-9 M of STS. The contrary effect was observed when 2h incubation was done in the presence in the medium of 10-12 M of STS.

The analogical changes were registered in the part of these investigations have been done with LM got at the stage of acute fit of the disease studied.

According to the results obtained all doses of STS as antioxidants demonstrate the normalizing effect against of super activated reactions of peroxideformation at acute period of FMF.

As obvious the results obtained in 2h incubation of EM got from erythrocytes of patients suffering with FMF at the stage of remission and of acute fit in the media with the different super low quantities of STS, are characterized by significant changes in qualitative composition and quantitative contents of PL. They are conditioned by tendency to normalize PL-PL interrelations and level of MDA in the biological systems studied. More pronounced changes were registered when 10-12 M of STS was used. Using the same doses of compound investigated in incubation media with LM, we got the analogical changes in PL and MDA

Table 1.
Dynamics of the content of cholinecontaining phospholipids (in ?g of lipid phosphorus/g of wet substance) in erythrocyte (A) and lymphocyte (B) membranes of patients with Familial Mediterranean Fever (FMF) at the stages of remission (1), acute fit (2) and effects of 10-6 M, 10-9 M and 10-12 M of sodium thyosulfate (STS) on this background.

Table 2.

Quantitative changes of the malonyl dialdehyde (in mM/ mg of protein) in erythrocyte (A) and lymphocyte (B) membranes of patients with Familial Mediterranean Fever (FMF) at the stages of remission (1), acute fit (2) and effects of 10-6 M, 10-9 M and 10-12 M of sodium thyosulfate (STS) on this background.

Conclusionmetabolism. The date obtained became very close to control indices. The changes demonstrate statistically unverified divergences. Moreover, the normalization of the standard levels of all representatives of PL was demonstrated with the exception of LPC concentrations both in EM and especially in LM. The contents of this category of PL in EM and LM stabilized on the definite level were statistically higher in compare with the control indexes. This fact justifies the opinion about the importance of the physiological role of lisoderivatives of PL in biological systems under the normal, extreme and particularly pathological states of the organism.

The results obtained have shown that acute fit and remission period of FMF are characterized by significant changes of the qualitative-quantitative composition of the different categories of PL in EM and especially in LM. The changes mentioned are accompanied with the pronounced activation of the free radical peroxidation of lipids in membranes mentioned both in ascorbate- and NADPH-dependent systems of peroxideformation. Using of the super low doses (10-12M) of the STS leads to the normalization in the membranes studied of the physiological rate of PL-PL interrelation with the simultaneous optimization of the normal concentration of the MDA. AT the same time the concentration of the LPC in compare with control remains on statistically high level in EM and LM even under the action of STS in super low doses (10-12M).


References:

  1. Агабалян А.С., Аветисян И.В., Карагезян К.Г. Влияние кальциевого прицепетата двуспиральной РНК на развитии нейротропного штамма вируса гриппа А в организме лабораторных животных // Нейрохимия, изд. РАН и НАН РА, Москва, 1998, т. 15, 2, с. 207-208.Бергельсон Л.Д., Дятловицкая Э.В. Итоги науки и техники. Серия “Иммунология” // М.: ВИНТИ, 1988, т. 22. с. 482-488.
  2. Grigoryan G.A., Harutyunyan V.M., Karageuzyan K.G., Zakaryan R.A., Melikoyan S.A. The role of interfractional transformation of the individual representatives of phospholipids in the rat blood erythrocytes upon the action of synthetic N-terminal fragments corresponding to immunomodulators at its treatment // International Small Conference “Braine and immune system”. Yerevan-Dilidjan, 1997, p. 2.
  3. Дятловицкая Э.В., Крюкова Е.В., Сускова В.С., Емец В.И., Мацуленко Е.Н., Шальков Б.И., Бергельсон Л.Д. Влияние ганглеозидов плаценты на бласттрансформацию и Т-супрессорную активность лимфоцитов человека // Иммунология, 1990, 2, с. 27-29.
  4. Дятловицкая Э.В. Сфинголипиды и злокачественный рост // Биохимия, 1995, т. 60, с. 843-850.
  5. Дятловицкая Э.В., Такиева Е.А., Леменовская О.Г., Сомова О.Г., Бергельсон Л.Д. Ганглиозиды GMиGDв опухолях желудка и молочной железы человека // Биохимия, 1990, 2, с. 27-29.
  6. Дятловицкая Э.В., Андреасян Г.О., Малых Я.Н. Церамиды и ганглеозиды яичников человека при старении // Биохимия, 1995, т. 60. вип. 8, с. 1302-1306.
  7. Дятловицкая Э.В., Андреасян Г.О., Малых Я.Н., Рылова С.Н. Шеддинг ганглеозидов и изменение биосинтеза церамидов в опухолях яичника человека // Биохимия, 1997, т 62, с. 651-656.
  8. Захарян Р.А., Тадевосян Ю.В., Азарян Н.Г., Карагезян К.Г. К Механизму активации процесса трансформации E-coli дс-РНК // Биол. Журнал Армении, Изд. НАН РА, 1988, т. 42, 2, с. 99-103.
  9. Karageuzyan K.G., Zakharyan R.A., Bakuntz K.A., Hovakimyan S.S. High specificity reception of double stranded RNA on neuronal plasmatic membrane // Giuseppe Percellati Foundation International Meeting of Neurochemical Aspects of Phospholipid Metabolism (Abstract). Italy, Perugia. 1988, p. 66.
  10. Karageuzyan K.G., Zakharyan R.A., Hovakimyan S.S., Vardanyan M.K. On the mechanism of transporting the exogenic DNA, RNA through plasmatic membrane of bone morrow cells // The 19th World Congress of the International Society for fat Research (ISF) and the 27th Annual Meeting Oil Chemists. Japan, Tokyo, 1988, Abstract, 3P12, p. 357.
  11. Karageuzyan K.G., Zakharyan R.A., Hakopyan Zh.I. The possible mechanisms of the inhibitory action of ds-RNA on the development of viral infection // FEBS, 19th Meeting, Rome, 1989, Abstract TH113.
  12. Карагезян К.Г., Карапетян Э.Т., Сафарян М.Д. Мембранные эффекты дс-РНК //  Республиканская конференция “Достижение физико-химическос биологии и особенности пути их внедрения (Тезисы докладов), Ереван, 1989, с. 11.
  13. Карагезян М.К. Изучение молекулярных механизмов токсических эффектов микотоксина зеараленона // Дисс. …. канд. биол. наук, 120 с.
5
Your rating: None Average: 5 (1 vote)
PARTNERS
 
 
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
image
Would you like to know all the news about GISAP project and be up to date of all news from GISAP? Register for free news right now and you will be receiving them on your e-mail right away as soon as they are published on GISAP portal.