Anacardic acid derived salicylates are inhibitors or activators of lipoxygenases

SUMMARY Despite recent advances in pharmacological treatment of psychiatric disorders, lithium salts remain frequently used, as they are effective and inexpensive alternatives, especially in the treatment of bipolar disorders. Their use is commonly associated with various endocrine disorders, mainly in thyroid and parathyroid function, and in mineral metabolism. This article aims at reviewing these potential endocrinopathies related to the use of lithium to make health care professionals aware and familiar with these possible complications when they follow up patients using this drug, and to make them able to monitor, identify and institute early and appropriate treatment. Arq Bras Endocrinol Metab. 2012;56(3):153-8

Endocrine disturbances related to the use of lithium Distúrbios endocrinológicos relacionados ao uso de lítio

1 Research Center for Innovative Technologies, Academy of Sciences of the Republic of Tajikistan, Dushanbe, Republic of Tajikistan 2 Institute of Avicenna’s Medicine and Pharmacology, Dushanbe, Republic of Tajikistan 3 University of Sorbonne Paris Cité-Paris 7, Lariboisière Hospital, INSERM U965, 75010 Paris, France 4 Central Scientific-Research Laboratory, Avicenna Tajik State Medical University, Dushanbe, Republic of Tajikistan

Molecular approach to determine the hot and cold temperaments in plants according avicenna concepts, the role of magnesium

Lipoxygenases (LOs) are known as one of the enzymes of lipid peroxidation. The majority of LOs are soluble enzymes and have affi nity to membranes. The enzyme translocation from a cytosol to a membrane surface is one of the stages of regulation of the amount of LO catalysis products in the cell. A sorption to the membrane surface is described for most LOs from plant and animal sources. This review presents the data about regulation of the LO activity by the lipid compounds – both natural and chemically modifi ed. Lipids might regulate the LO activity through: protein-lipid interactions of C2 domain with the membrane, changes in the enzyme affi nity, the LOs translocation, allosteric regulation, increase in the selectivity towards substrates. The regulatory effect of active compound on the enzyme activity depends on the lipophilicity of effectors. Considering the LO activity it is necessary to take into account the enzyme microenvironment and its infl uence on the range of the LO products.

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Lipoxygenase regulation in vivo and in vitro by lipid compounds

It has been shown that calix[4]arene C-99 inhibited myosin subfragment-1 ATPase of myometrium. This inhibition is noncompetitive as to ATP and Mg2+. At the same time, this compound reduces the seeming enzymatic hydrolysis maximum rate of nucleoside triphosphate with respect to ATP and Mg2+. With the help of computer design the interaction of mentioned calix[4]arene with myosin subfragment-1 of myometrium has been investigated. Several mechanisms involved in the calix[4]arene C-99 inhibition of myosin head ATPase were supposed and participation of hydrogen, hydrophobic and electrostatic interactions in these mechanisms was discussed.

[Kinetic regularities and mechanisms of action of calix[4]arene C-99 on ATPase activity of myosin subfragment-1 of myometrium].

Investigation the influence of calyx[4]arenes C-90, C-91, C-97 and C-99 (codes are indicated) on the enzymatic activity of four functionally different Mg2+ -dependent ATPases from smooth muscle of the uterus: actomyosin ATPase, transporting Ca2+, Mg2+ -ATPase, ouabain-sensible Na+, K+ -ATPase and basal Mg2+ -ATPase. It was shown that calixarenes C-90 and C-91 in concentration 100 microM act multidirectionally on the functionally different Mg2+ -dependent ATP-hydrolase enzymatic systems. These compounds activate effectively the actomyosin ATPase (Ka = 52 +/- 11 microM [Ukrainian character: see text] 8 +/- 2 microM, accordingly), at the same time calixarene C-90 inhibited effectively activity of transporting Ca2+, Mg2+ -ATPase of plasmatic membranes (I(0,5) = 34.6 +/- 6.4 microM), but influence on membrane-bound Na+, K+ -ATPase and basal Mg2+ -ATPase. Calixarene C-91 reduce effectively basal Mg2+ -ATPase activity, insignificantly activating Na+, K+ -ATPase but has no influence on transporting Ca2+, Mg2+ -ATPase activity of plasmatic membranes. Calixarenes C-97 and C-99 (100 microM), which have similar structure, have monodirectional influence on activity of three functionally different Mg2+-dependent ATPases of the myometrium: actomyosin ATPase and two ATPases, that related to the ATP-hydrolases of P-type--Ca2+, Mg2+ -ATPase and Na+, K+ -ATPase of plasmatic membranes. Basal Mg2+ -ATPase is resistant to the action of these two connections. Results of comparative experiments that were obtained by catalytic titration of calixarenes C-97 and C-99 by actomyosin ATPase (I(0,5) = 88 +/- 9 and 86 +/- 8 microM accordingly) and Na+, K+ -ATPase from plasmatic membranes (I(0,5) = 33 +/- 4 and 98 +/- 8 nM accordingly) indicate to the considerably more sensitiveness of Na+, K+ -ATP-ase to these calixarenes than ATPase of contractile proteins. Thus, it is shown that calixarenes have influence on activity of a number of important enzymes, involved in functioning of the smooth muscle of the uterus and related to energy-supplies of the process of the muscle contracting and support of intracellular ionic homeostasis. The obtained results can be useful in further researches, directed at the use of calixarenes as pharmaceutical substance, able to normalize the contractile function of the uterus at some pregnancy pathologies in women's.

[Comparative study of calixarene effect on Mg2+ -dependent ATP-hydrolase enzymatic systems from smooth muscle cells of the uterus].

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Тhiacalix[4]arene phosphonate C-800 as a novel fluorescent probe for zinc in living cells

The discovery of compounds that might modify myometrial contractility is an important area of researches. In our previous experiments, we found that some representatives of macrocyclic compounds family – calix[4]arenes – can modify the enzymatic and transport activity of membrane-bound cation-transport ATP hydrolases. The aim of this work was to study and compare the effect of calix[4]arene C-107 on the enzymatic activities of mg2+-dependent aTPases of the uterine smooth muscle, namely: ouabain-sensitive Na+,k+-aTPase, plasma membrane ca2+-independent “basal” mg2+-aTPase, aTPase of the actomyosin complex and myosin subfragment-1, with effect on the contractile activity of the myometrium. It was shown that calix[4]arene C-107 efficiently inhibited myometrium Na+,k+-aTPase (I50 = 54 ± 6 nm) selectively to other aTP-hydrolases of the plasma membrane and simultaneously activated the enzymatic activity of the myosin aTPase of smooth muscles (a50 = 9.6 ± 0.7 μM). Such reciprocal biochemical effects led to the stimulation of the smooth muscle contractile activity that was demonstrated by the tensometric method using different isolated smooth muscles. Calix[4]arene С-107 was shown to stimulate the increase of the tonic component of myometrium contractions induced by oxytocin, as well as contractions of the caecum muscles induced by high-potassium solution or acetylcholine, and to maintain increased tension for a long time. Thus, calix[4]arene C-107 is a prospective compound for enhancing the smooth muscle basal tone and/or contraction in case of hypotonic dysfunctions.

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Inhibition of Na(+),K(+)-ATPase and activation of myosin ATPase by calix[4]arene C-107 cause stimulation of isolated smooth muscle contractile activity

Calix[4]arenes are cup-like macrocyclic (polyphenolic) compounds, they are regarded as promising molecular "platforms" for the design of new physiologically active compounds. We have earlier found that calix[4]arene C-99 inhibits the ATPase activity of actomyosin and myosin subfragment-1 of pig uterus in vitro. The aim of this study was to investigate the interaction of calix[4]arene C-99 with myosin from rat uterine myocytes. It was found that the ATPase activity of myosin prepared from pre-incubated with 100 mM of calix[4]arene C-99 myocytes was almost 50% lower than in control. Additionally, we have revealed the effect of calix[4]arene C-99 on the subcellular distribution of actin and myosin in uterus myocytes by the method of confocal microscopy. This effect can be caused by reorganization of the structure of the contractile smooth muscle cell proteins due to their interaction with calix[4]arene. The obtained results demonstrate the ability of calix[4]arene C-99 to penetrate into the uterus muscle cells and affect not only the myosin ATPase activity, but also the structure of the actin and myosin filaments in the myometrial cells. Demonstrated ability of calix[4]arene C-99 can be used for development of new pharmacological agents for efficient normalization of myometrial contractile hyperfunction.

Labyntseva Rd

Papers

[Comparative study of calixarene effect on Mg2+ -dependent ATP-hydrolase enzymatic systems from smooth muscle cells of the uterus].

[Kinetic regularities and mechanisms of action of calix[4]arene C-99 on ATPase activity of myosin subfragment-1 of myometrium].

Тhiacalix[4]arene phosphonate C-800 as a novel fluorescent probe for zinc in living cells

Inhibition of Na(+),K(+)-ATPase and activation of myosin ATPase by calix[4]arene C-107 cause stimulation of isolated smooth muscle contractile activity

CALIX[4]ARENE C-99 INHIBITS MYOSIN ATPase ACTIVITY AND CHANGES THE ORGANIZATION OF CONTRACTILE FILAMENTS OF MYOMETRIUM.