Published: Ecological Studies, Hazards, Solutions, 2013, vol.19, p. 9-28.
TOXICOLOGY, BIOPHYSICS. FROM FUNDAMENTAL BIOMEDICAL RESEARCH TO APPLICATIONS. SOME RESULTS AND BIBLIOGRAPHY
Orlov S.N., Kotelevtsev S.V., Novikov K.N., Selishcheva A.A., Akimova O.A., Ostroumov S.A.
M.V.Lomonosov Moscow State University, Vorobyevy Gory, Moscow; Universite de Montreal;
The goal of this publication is to present some of results of experimental research of interdisciplinary topics of life science in the Laboratory of Physico-Chemistry of biological membranes. The material is organized into 6 sections.
1. Results of S.N. Orlov and co-authors, examples:
Cell volume and monovalent ion transporters: their role in triggering and progression of the cell death machinery (Orlov S.N., et al., 2013).
Apoptosis involves many aspects of biochemical and biophysical phenomena in cell biology, including monovalent ion transfer across biological membranes. The studies of interconnections among those phenomena is of a significant interest.
Cell death is accompanied by the dissipation of electrochemical gradients of monovalent ions across the plasma membrane that, in turn, affects cell volume via modulation of intracellular osmolyte content. In various cell types, apoptotic and necrotic stimuli caused cell shrinkage and swelling, respectively. Thermodynamics predicts a cell type-specific rather than a ubiquitous impact of monovalent ion transporters on volume perturbations in dying cells, suggesting their diverse roles in the cell death machinery. Indeed, some recent data showed that apoptotic collapse may occur in the absence of cell volume changes and even follow cell swelling rather than shrinkage.
Moreover, side-by-side with cell volume adjustment, monovalent ion transporters contribute to cell death machinery engagement independently of volume regulation via cell type-specific signalling pathways. Thus, inhibition of Na+,K+-ATPase by cardiotonic steroids (CTS) rescues rat vascular smooth muscle cells from apoptosis via a novel Na+i,K+i-mediated, Ca2+i-independent mechanism of excitation-transcription coupling. By contrast, CTS kill renal epithelial cells independently of Na+,K+-ATPase inhibition and increased [Na+]i/[K+]i ratio.
The molecular origin of [Na+]i/[K+]i sensors involved in the inhibition of apoptosis as well as upstream intermediates of Na+i/K+i-independent death signalling triggered by cardiotonic steroids (CTS) remain a subject for further research.
(based on: Orlov SN, Platonova AA, Hamet P, Grygorczyk R. Cell volume and monovalent ion transporters: their role in triggering and progression of the cell death machinery. Am J Physiol Cell Physiol. 2013 Apr 24. [Epub ahead of print]).
Bibliography of publications of Orlov S.N., selected:
1. Orlov SN, Platonova AA, Hamet P, Grygorczyk R. Cell volume and monovalent ion transporters: their role in triggering and progression of the cell death machinery. // Am J Physiol Cell Physiol. 2013 Apr 24. [Epub ahead of print] PMID: 23615964
2. Parshina EY, Yusipovich AI, Platonova AA, Grygorczyk R, Maksimov GV, Orlov SN. Thermal inactivation of volume-sensitive K(+),Cl (-) cotransport and plasma membrane relief changes in human erythrocytes. // Pflugers Arch. 2013 Feb 2. [Epub ahead of print] PMID: 23377567 [PubMed - as supplied by publisher]
3. Orlov SN, Koltsova SV, Tremblay J, Baskakov MB, Hamet P. NKCC1 and hypertension: role in the regulation of vascular smooth muscle contractions and myogenic tone. // Ann Med. 2012 Jun;44 Suppl 1:S111-8. doi: 10.3109/07853890.2011.653395. Review. PMID: 22713139 [PubMed - indexed for MEDLINE]
4. Koltsova SV, Trushina Y, Haloui M, Akimova OA, Tremblay J, Hamet P, Orlov SN. Ubiquitous [Na+]i/[K+]i-sensitive transcriptome in mammalian cells: evidence for Ca(2+)i-independent excitation-transcription coupling. // PLoS One. 2012;7(5):e38032. doi: 10.1371/journal.pone.0038032. Epub 2012 May 29. PMID: 22666440 [PubMed - indexed for MEDLINE]
5. Koltsova SV, Akimova OA, Kotelevtsev SV, Grygorczyk R, Orlov SN. Hyperosmotic and isosmotic shrinkage differentially affect protein phosphorylation and ion transport. // Can J Physiol Pharmacol. 2012;90(2):209-217. doi: 10.1139/y11-119. Epub 2012 Feb 2. PMID: 22300272 [PubMed - indexed for MEDLINE]
6. Platonova A, Koltsova SV, Hamet P, Grygorczyk R, Orlov SN. Swelling rather than shrinkage precedes apoptosis in serum-deprived vascular smooth muscle cells. // Apoptosis. 2012;17(5):429-438. doi: 10.1007/s10495-011-0694-x. PMID: 22249286 [PubMed - indexed for MEDLINE]
7. Akimova OA, Van Huysse J, Tremblay J, Orlov SN. Low efficiency of functional translation of ouabain-resistant α2-Na(+),K(+)-ATPase mRNA in C7-MDCK epithelial cells. // Can J Physiol Pharmacol. 2012 Jan;90(1):83-8. doi: 10.1139/y11-113. Epub 2011 Dec 21. PMID: 22188474 [PubMed - indexed for MEDLINE]
8. Orlov SN. NKCC1 as an epigenetically regulated transporter involved in blood pressure elevation with age. // Am J Hypertens. 2011 Dec;24(12):1264. doi: 10.1038/ajh.2011.150. PMID: 22083447 [PubMed - indexed for MEDLINE]
9. Yusipovich AI, Zagubizhenko MV, Levin GG, Platonova A, Parshina EY, Grygorzcyk R, Maksimov GV, Rubin AB, Orlov SN. Laser interference microscopy of amphibian erythrocytes: impact of cell volume and refractive index. // J Microsc. 2011 Dec;244(3):223-229. doi: 10.1111/j.1365-2818.2011.03516.x. Epub 2011 Oct 17. PMID: 21999139 [PubMed - indexed for MEDLINE]
10. Orlov SN, Hamet P. [The search for a sensor of intracellular sodium involved in pathogenesis of hypertensive disease]. // Vestn Ross Akad Med Nauk. 2011;(7):45-50. Review. Russian. PMID: 21899092 [PubMed - indexed for MEDLINE]
11. Orlov SN, Churilov LP, Stroev IuI. [What is pathophysiology nowadays? The reflections of the participants of ISP-2010 Congress in Montreal]. // Patol Fiziol Eksp Ter. 2011 Apr-Jun;(2):3-12. Russian. PMID: 21847827 [PubMed - indexed for MEDLINE]
12. Platonova A, Koltsova S, Maksimov GV, Grygorczyk R, Orlov SN. The death of ouabain-treated renal epithelial C11-MDCK cells is not mediated by swelling-induced plasma membrane rupture. // J Membr Biol. 2011 Jun;241(3):145-54. doi: 10.1007/s00232-011-9371-9. Epub 2011 May 17. PMID: 21584679 [PubMed - indexed for MEDLINE]
13. Koltsova SV, Platonova A, Maksimov GV, Mongin AA, Grygorczyk R, Orlov SN. Activation of P2Y receptors causes strong and persistent shrinkage of C11-MDCK renal epithelial cells.// Am J Physiol Cell Physiol. 2011;301(2):C403-412. doi: 10.1152/ajpcell.00018.2011. Epub 2011 May 11. PMID: 21562307 [PubMed - indexed for MEDLINE]
14. Kol'tsova SV, Baskakov MB, Orlov SN. [Myogenic tone of blood vessels in health and disease: role of purinergic signaling system and Na+, K+ 2Cl+ cotransport]. // Patol Fiziol Eksp Ter. 2010 Oct-Dec;(4):3-10. Review. Russian. PMID: 21395111 [PubMed - indexed for MEDLINE]
15. Koltsova SV, Trushina YA, Akimova OA, Hamet P, Orlov SN. Molecular origin of Na(+)/Li(+) exchanger: Evidence against the involvement of major cloned erythrocyte transporters. // Pathophysiology. 2011 Jun;18(3):207-13. doi: 10.1016/j.pathophys.2010.12.001. Epub 2011 Jan 17. PMID: 21247741 [PubMed]
16. Akimova OA, Lopina OD, Rubtsov AM, Hamet P, Orlov SN. Investigation of mechanism of p38 MAPK activation in renal epithelial cell from distal tubules triggered by cardiotonic steroids.// Biochemistry (Mosc). 2010;75(8):971-978. PMID: 21073417 [PubMed - indexed for MEDLINE]
17. Malekin SI, Kotelevtsev SV, Gavrilova SA, Fadyukova OE, Golubeva AV, Grinchenko MI, Koshelev VB, Kotelevtsev YV, Hamet P, Orlov SN. Long-term normalization of blood pressure in SHR and 1-kidney 1-clip rats by synthetic precursor of stable PAF analogue without systemic effects in normotensive rats.//Pathophysiology. 2011 Apr;18(2):151-157. doi: 10.1016/j.pathophys.2010.08.001.PMID: 20888741 [PubMed]
18. Rebrov VG, Usanov DA, Usanov AD, Kotelevtsev SV, Orlov SN. Low-frequency magnetic radiation leads to the broadening of valent bonds in protein infrared spectra. // Pathophysiology. 2011 Apr;18(2):121-3. doi: 10.1016/j.pathophys.2010.05.001. Epub 2010 May 26. PMID: 20537876 [PubMed]
19. Orlov SN, Tremblay J, Hamet P. NKCC1 and hypertension: a novel therapeutic target involved in the regulation of vascular tone and renal function. // Curr Opin Nephrol Hypertens. 2010 Mar;19(2):163-168. doi: 10.1097/MNH.0b013e3283360a46. Review. PMID: 20061948 [PubMed - indexed for MEDLINE]
20. Orlov SN, Gossard F, Pausova Z, Akimova OA, Tremblay J, Grim CE, Kotchen JM, Kotchen TA, Gaudet D, Cowley AW, Hamet P. Decreased NKCC1 activity in erythrocytes from African Americans with hypertension and dyslipidemia. // Am J Hypertens. 2010 Mar;23(3):321-326.
21. Maximov G.V., Orlov S.N. [book] 1994 Transport of calcium ions under axon functioning: mechanisms and regulation. Moscow State Univ. Publ., Moscow, 87 p.
2. Results of S.V.Kotelevtsev and co-authors, examples.
Mutagenicity and genotoxicity of the sewage and industrial effluents (Glazer V.M., Kotelevtsev S.V., et al., 1990)
The Ames test was applied for the analysis of industrial effluents from cellulose production and sewage waters varying in the degree of purification. The method used a metabolic activation system from rat and fish liver with Salmonella strains TA 98 and TA 100. As a result, a strong direct mutagenic effect on strain TA 100 was discovered in samples which were taken after cellulose chlorination.
The multistage procedure of sewage water purification allows to remove practically completely the mutagenic substances. A simultaneous study of cytotoxic effects of industrial effluents on mammalian cells discovered that the mutagenic activity was exhibited in not toxic concentrations. The results demonstrated the urgency of a regular biological control of the genotoxicity of industrial effluents from the sulfate production of cellulose.
This summary is based on the publication: Glazer VM, Kotelevtsev SV, Stepanova LI, Abilev SK, Buevich GV, Beĭm AM. An evaluation in the Ames test of the mutagenicity of the sewage and industrial effluents from the Baikal Paper and Pulp Combine. // Nauchnye Doki Vyss Shkoly Biol Nauki. 1990;(1):101-109.
Bibliography of publications of S.V.Kotelevtsev, selected.
1. Orlov S.N., Thorin-Trescases N., Tremblay J., Hamet P., Kotelevtsev S.V. INVERSION OF THE INTRACELLULAR NA+/K+ RATIO BLOCKS APOPTOSIS IN VASCULAR SMOOTH MUSCLE AT A SITE UPSTREAM OF CASPASE-3. // Journal of Biological Chemistry. 1999. Т. 274. № 23. С. 16545-16552.
2. Lindström-Seppä P., Huuskonen S., Räänen T., Hänninen O., Kotelevtsev S., Stepanova L., Mikkelson P. TOXICITY AND MUTAGENICITY OF WASTE WATERS FROM BAIKALSK PULP AND PAPER MILL: EVALUATION OF POLLUTANT CONTAMINATION IN LAKE BAIKAL. // Marine Environmental Research. 1998. Т. 46. № 1-5. С. 273-277.
3. Whitehead A., Anderson S.L., Kuivila K.M., Orlando J.L., Kotelevtsev S. GENOTOXICITY IN NATIVE FISH ASSOCIATED WITH AGRICULTURAL RUNOFF EVENTS. //Environmental Toxicology and Chemistry. 2004. Т. 23. № 12. С. 2868-2877.
4.Orlov S.N., Aksentsev S.L., Kotelevtsev S.V. EXTRACELLULAR CALCIUM IS REQUIRED FOR THE MAINTENANCE OF PLASMA MEMBRANE INTEGRITY IN NUCLEATED CELLS. //Cell Calcium. 2005. Т. 38. № 1. С. 53-57.
5. Akimova O.A., Poirier M., Hamet P., Orlov S.N., Kotelevtsev S.V. THE DEATH OF OUABAIN-TREATED RENAL EPITHELIAL CELLS: EVIDENCE AGAINST ANOIKIS OCCURRENCE. // Apoptosis. 2008. Т. 13. № 5. С. 670-680.
6. Orlov S.N., Grygorczyk R., Kotelevtsev S.V. DO WE KNOW THE ABSOLUTE VALUES OF INTRACELLULAR FREE CALCIUM CONCENTRATION? // Cell Calcium. 2003. Т. 34. № 6. С. 511-515.
7. Павлов Д.С., Смуров А.В., Ильяш Л.В., Маторин Д.Н., Клюев Н.А., Котелевцев С.В., Румак В.С., Смурова Т.Г. СОВРЕМЕННОЕ СОСТОЯНИЕ КОРАЛЛОВЫХ РИФОВ ЗАЛИВА НЯЧАНГ (ЮЖНЫЙ ВЬЕТНАМ) И ВОЗМОЖНЫЕ ПРИЧИНЫ НЕБЛАГОПОЛУЧИЯ СРЕДЫ ОБИТАНИЯ СКЛЕРАКТИНИЙ. // Биология моря. 2004. Т. 30. № 1. С. 60-67.
8. Остроумов С.А., Шестакова Т.В., Котелевцев С.В., Соломонова Е.А., Головня Е.Г., Поклонов В.А. ПРИСУТСТВИЕ МАКРОФИТОВ В ВОДНОЙ СИСТЕМЕ УСКОРЯЕТ СНИЖЕНИЕ КОНЦЕНТРАЦИЙ МЕДИ, СВИНЦА И ДРУГИХ ТЯЖЕЛЫХ МЕТАЛЛОВ В ВОДЕ. // Водное хозяйство России: проблемы, технологии, управление. 2009. № 2. С. 58-66.
9. Koltsova S.V., Tremblay J., Hamet P., Orlov S.N., Kotelevtsev S.V. EXCITATION-CONTRACTION COUPLING IN RESISTANCE MESENTERIC ARTERIES: EVIDENCE FOR NKCC1-MEDIATED PATHWAY // Biochemical and Biophysical Research Communications. 2009. Т. 379. № 4. С. 1080-1083.
10. Остроумов С.А., Котелевцев С.В., Шестакова Т.В., Колотилова Н.Н., Поклонов В.А., Соломонова Е.А. НОВОЕ О ФИТОРЕМЕДИАЦИОННОМ ПОТЕНЦИАЛЕ: УСКОРЕНИЕ СНИЖЕНИЯ КОНЦЕНТРАЦИЙ ТЯЖЕЛЫХ МЕТАЛЛОВ (PB, CD, ZN, CU) В ВОДЕ В ПРИСУТСТВИИ ЭЛОДЕИ. // Экологическая химия. 2009. № 18. С. 111.
11. Koltsova S.V., Lavoie J.L., Tremblay J., Grygorczyk R., Hamet P., Orlov S.N., Maximov G.V., Kotelevtsev S.V. MYOGENIC TONE IN MOUSE MESENTERIC ARTERIES: EVIDENCE FOR P2Y RECEPTOR-MEDIATED, NA+, K+, 2CL- COTRANSPORT-DEPENDENT SIGNALING. // Purinergic Signalling. 2009. Т. 5. № 3. С. 343-349.
12. Kotelevtsev S.V., Hanninen O.O.P., Lindström-Seppa P.A., Huskon S.E., Stepanova L.I., Glaser V.M., Beim A.M. Mutagenicity of bleached and unbleached effluents from Baikalsk pulp and paper mill at Lake Baikal, Russia. Aquatic Ecosystem Health and Management. 2000. Т. 3. С. 95-104.
13. Stepanova L.I., Lindström-Seppä P., Hänninen O.O.P., Kotelevtsev S.V., Glaser V.M., Novikov C.N. LAKE BAIKAL: BIOMONITORING OF PULP AND PAPER MILL WASTE WATER. // Aquatic Ecosystem Health and Management. 2000. Т. 3. С. 259.
14. Stepanova L.I., Glaser V.M., Savinova T.I., Kotelevtsev S.V., Savva D. ACCUMULATION OF MUTAGENIC XENOBIOTICS IN FRESH WATER (LAKE BAIKAL) AND MARINE (HORNOYA ISLAND) ECOSYSTEMS. // Ecotoxicology. 1999. Т. 8. № 2. С. 83-96.
15. Pavlov D.S., Kluyev N.A., Rumak V.S., Smurov A.V., Smurova T.G., Il'yash L.V., Matorin D.N., Kotelevtsev S.V. PRESENT-DAY STATE OF CORAL REEFS OF NHA TRANG BAY (SOUTHERN VIETNAM) AND POSSIBLE REASONS FOR THE DISTURBANCE OF HABITATS OF SCLERACTINIAN CORALS. // Russian Journal of Marine Biology. 2004. Т. 30. № 1. С. 43-50.
16. Саратовских Е.А., Глазер В.М., Костромина Н.Ю., Котелевцев С.В. ГЕНОТОКСИЧНОСТЬ ПЕСТИЦИДОВ В ТЕСТЕ ЭЙМСА И ИХ СПОСОБНОСТЬ К ОБРАЗОВАНИЮ КОМПЛЕКСОВ С ДНК. // Экологическая генетика. 2007. Т. V. № 3. С. 46-54.
17. Котелевцев С.В., Пономарева Л.В. ИНДУКЦИЯ С ПОМОЩЬЮ ПОЛИЦИКЛИЧЕСКИХ УГЛЕВОДОРОДОВ АКТИВНОСТИ МОНООКСИГЕНАЗ В ТКАНЯХ РЫБ И ЕЕ ИСПОЛЬЗОВАНИЕ ДЛЯ БИОМОНИТОРИНГА ЗАГРЯЗНЕННЫХ ВОД. //Экспериментальная онкология. 1987. № 5. С. 46. 18.
18. Котелевцев С.В., Степанова Л.И. БИОТЕСТИРОВАНИЕ КАНЦЕРОГЕННЫХ И МУТАГЕННЫХ СОЕДИНЕНИЙ В ВОДНЫХ СИСТЕМАХ. //Российский химический журнал. 1994. Т. 38. С. 42.
19. Котелевцев С.В., Пономарева Л.В., Новиков К.Н. ИММУНОХИМИЧЕСКИЙ АНАЛИЗ ИНДУКЦИИ ИЗОФОРМ ЦИТОХРОМА Р-450 В ПЕЧЕНИ ПРЕСНОВОДНЫХ РЫБ 3-МЕТИЛХОЛАНТРЕНОМ, B-НАФТАФЛАВОНОМ И АРОХЛОРОМ 1254. // Биологические науки. 1990. № 5. С. 23.
20. Kotelevtzev S.V., Nagdaliev F.F., Sadchikov A.P. Bio-assay and bioindication at ecological analysis of the environment. Publishers: Alteks, Moscow, 2011, 174 p.
21. Kotelevtsev S.V., Matorin D.N., Sadchikov A.P. Ecological-Toxicological analysis of plant communities in aquatic ecosystems. Altex Press, Moscow. 2012. 182 p.
3. Results of K.N.Novikov and co-authors, examples.
Changes in chemiluminescence of whole blood of chronic obstructive pulmonary disease (COPD) patients treated with Hypoxen; effects of fullerenes (C₆₀ ) on blood chemiluminescence (Novikov et al., 2012).
Summary of a research project. BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an inflammatory disease associated with reactive oxygen species (ROS) production. The aim of this study was to evaluate the effect of Hypoxen treatment and the effect of fullerenes (HyFnC₆₀ ) on reactive oxygen species (ROS) production in patients' blood. MATERIAL/METHODS: Reactive oxygen species ROS production in blood was estimated using chemiluminescence (CL) measurement with chemiluminescence amplifiers, namely: luminol (LM), LM + zymosan (ZM) or lucigenin (LC) in the presence or absence of hydrated fullerenes (HyFnC₆₀) added to blood in low concentrations. RESULTS: In all the patients with chronic obstructive pulmonary disease (COPD) in remission phase with Hypoxen prescription, the LM-dependent CL (LM-CL) with ZM and LC-enhanced CL (LC-CL) decreased after the treatment. Parameters of chemiluminescence and effects of fullerenes (HyFnC₆₀ ) upon them depended on blood state. Addition of fullerenes HyFnC₆₀ to blood decreased data scattering and helped to improve discrimination between different groups of patients. Using the discriminator analysis, we found the most important time-points in the kinetic curves of chemiluminescence for classification of patients into groups (eg, COPD patients before and after treatment with Hypoxen; patients' blood with different sensitivity to HyFnC₆₀ concentration). CONCLUSIONS: Monitoring of chemiluminescence of non-diluted whole blood in chronic obstructive pulmonary disease (COPD) patients can be used for the estimation of the Hypoxen efficiency in complex therapy. Addition of fullerenes HyFnC₆₀ to blood increases sensitivity of the method.
This summary is based on:
Novikov KN, Berdnikova NG, Novikov AK, Lyusina OY, Muhitova OG, Yablonskaya OI, Minh HD, Voeikov VL. Changes in chemiluminescence of whole blood of COPD patients treated with Hypoxen and effects of C₆₀ fullerenes on blood chemiluminescence. // Med Sci Monit. 2012; 18(2): BR76-83.
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