Trimethylamine N-oxide suppresses the activity of the actomyosin motor
Abstract
Background During actomyosin interactions, the transduction of energy from ATP hydrolysis to motility seems to occur with the modulation of hydration. Trimethylamine N-oxide (TMAO) perturbs the surface of proteins by altering hydrogen bonding in a manner opposite to that of urea. Hence, we focus on the effects of TMAO on the motility and ATPase activation of actomyosin complexes.Methods Actin and heavy meromyosin (HMM) were prepared from rabbit skeletal muscle. Structural changes in HMM were detected using fluorescence and circular dichroism spectroscopy. The sliding velocity of rhodamine-phalloidin-bound actin filaments on HMM was measured using an in vitro motility assay. ATPase activity was measured using a malachite green method.Results Although TMAO, unlike urea, stabilized the HMM structure, both the sliding velocity and ATPase activity of acto-HMM were considerably decreased with increasing TMAO concentrations from 0-1.0M. Whereas urea-induced decreases in the structural stability of HMM were recovered by TMAO, TMAO further decreased the urea-induced decrease in ATPase activation. Urea and TMAO were found to have counteractive effects on motility at concentrations of 0.6M and 0.2M, respectively.Conclusions The excessive stabilization of the HMM structure by TMAO may suppress its activities; however, the counteractive effects of urea and TMAO on actomyosin motor activity is distinct from their effects on HMM stability.General significance The present results provide insight into not only the water-related properties of proteins, but also the physiological significance of TMAO and urea osmolytes in the muscular proteins of water-stressed animals.
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Excess TMAO in the absence of a perturbant can inhibit protein function as a result of overstabilization.
“Both up-and down-regulation are important because excess TMAO in the absence of a perturbant (such as urea or pressure) can inhibit protein function as a result of overstabilization (19,27).”
From Marine fish may be biochemically constrained from inhabiting the deepest ocean depths (2014) · cites this paper as [27]
High concentrations of TMAO may impair function, as reported for actomyosin motor activity.
“By contrast, high concentrations of TMAO may at times also impair function, as was reported for the activity of the actomyosin motor142.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [142]
Cites
Living with Water Stress: Evolution of Osmolyte Systems
Yancey, P. H., Clark, M. E., Hand, S. C., Bowlus, R. D., & Somero, G. N. (1982) · Science · doi:10.1126/science.7112124 · Cited by 3,724 · see citing works
[18] Purification of muscle actin
Pardee, J. D., & Aspudich, J. (1982) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(82)85020-9 · Cited by 1,190 · see citing works
[7] Preparation of myosin and its subfragments from rabbit skeletal muscle
Margossian, S. S., & Lowey, S. (1982) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(82)85009-x · Cited by 981 · see citing works
Zou, Q., Bennion, B. J., Daggett, V., & Murphy, K. P. (2002) · Journal of the American Chemical Society · doi:10.1021/ja004206b · Cited by 446 · see citing works
Bennion, B. J., & Daggett, V. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308633101 · Cited by 310 · see citing works
Entropic Stabilization of Proteins by TMAO
Cho, S. S., Reddy, G., Straub, J. E., & Thirumalai, D. (2011) · The Journal of Physical Chemistry B · doi:10.1021/jp207289b · Cited by 198 · see citing works
Auton, M. T., Bolen, D. W., & Rösgen, J. (2008) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.22103 · Cited by 175 · see citing works
Structure and Interaction in Aqueous Urea−Trimethylamine-N-oxide Solutions
Paul, S., & Patey, G. N. (2007) · Journal of the American Chemical Society · doi:10.1021/ja0685506 · Cited by 158 · see citing works
Athawale, M. V., Dordick, J. S., & Garde, S. (2005) · Biophysical Journal · doi:10.1529/biophysj.104.056671 · Cited by 153 · see citing works
Counteraction of Urea by Trimethylamine N-Oxide Is Due to Direct Interaction
Meersman, F., Bowron, D. T., Soper, A. K., & Koch, M. H. J. (2009) · Biophysical Journal · doi:10.1016/j.bpj.2009.08.017 · Cited by 135 · see citing works
Baskakov, I. V., Wang, A., & Bolen, D. W. (1998) · Biophysical Journal · doi:10.1016/s0006-3495(98)77972-x · Cited by 133 · see citing works
Counteracting Osmolyte Trimethylamine N-Oxide Destabilizes Proteins at pH below Its pK
Singh, R., Haque, I., & Ahmad, F. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m410716200 · Cited by 122 · see citing works
Panuszko, A., Bruździak, P., Zielkiewicz, J., Wyrzykowski, D., & Stangret, J. (2009) · The Journal of Physical Chemistry B · doi:10.1021/jp904001m · Cited by 119 · see citing works
Thermodynamic analysis of muscle ATPase mechanisms.
Kodama, T. (1985) · Physiological Reviews · doi:10.1152/physrev.1985.65.2.467 · Cited by 114 · see citing works
Myosin-induced volume increase of the hyper-mobile water surrounding actin filaments
Suzuki, M., Kabir, S. R., Siddique, M. S. P., Nazia, U. S., Miyazaki, T., & Kodama, T. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.07.111 · Cited by 46 · see citing works
Kinetics of adenosine triphosphate hydrolysis by shortening myofibrils from rabbit psoas muscle.
Ohno, T., & Kodama, T. (1991) · The Journal of Physiology · doi:10.1113/jphysiol.1991.sp018773 · Cited by 44 · see citing works
4,4'-Bis (1-anilinonaphthalene 8-sulfonate) (bis-ANS): a new probe of the active site of myosin.
Takashi, R., Tonomura, Y., & Morales, M. F. (1977) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.74.6.2334 · Cited by 42 · see citing works
Betaine protects urea‐induced denaturation of myosin subfragment‐1
Ortiz‐Costa, S., Sorenson, M. M., & Sola‐Penna, M. (2008) · FEBS Journal · doi:10.1111/j.1742-4658.2008.06487.x · Cited by 39 · see citing works
Factors affecting counteraction by methylamines of urea effects on aldose reductase
Burg, M. B., Peters, E. M., Bohren, K. M., & Gabbay, K. H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.11.6517 · Cited by 38 · see citing works
Counteracting effects of urea and methylamines in function and structure of skeletal muscle myosin
Ortiz‐Costa, S., Sorenson, M. M., & Sola‐Penna, M. (2002) · Archives of Biochemistry and Biophysics · doi:10.1016/s0003-9861(02)00565-9 · Cited by 36 · see citing works
Kamen, D. E., & Woody, R. W. (2001) · Protein Science · doi:10.1110/ps.19801 · Cited by 35 · see citing works
Osmotic pressure probe of actin-myosin hydration changes during ATP hydrolysis
Highsmith, S. R., Duignan, K., Cooke, R., & Cohen, J. (1996) · Biophysical Journal · doi:10.1016/s0006-3495(96)79852-1 · Cited by 32 · see citing works
4,4′-Dianilino-1,1′-binaphthyl-5,5′-sulfonate, a novel molecule having chaperone-like activity
Fu, X., Zhang, X., & Chang, Z. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.01.164 · Cited by 32 · see citing works
Effect of Osmolytes on Protein Dynamics in the Lactate Dehydrogenase-Catalyzed Reaction
Zhadin, N., & Callender, R. H. (2011) · Biochemistry · doi:10.1021/bi1018545 · Cited by 30 · see citing works
Influence of Ionic Strength on the Actomyosin Reaction Steps in Contracting Skeletal Muscle Fibers
Iwamoto, H. (2000) · Biophysical Journal · doi:10.1016/s0006-3495(00)76850-0 · Cited by 26 · see citing works
Myosin cleft closure determines the energetics of the actomyosin interaction
Takács, B., O'Neall-Hennessey, E., Hetényi, C., Kardos, J., Szent‐Györgyi, A. G., & Kovács, M. (2010) · The FASEB Journal · doi:10.1096/fj.10-164871 · Cited by 24 · see citing works
Link between the Enzymatic Kinetics and Mechanical Behavior in an Actomyosin Motor
Amitani, I., Sakamoto, T., & Ando, T. (2001) · Biophysical Journal · doi:10.1016/s0006-3495(01)76022-5 · Cited by 22 · see citing works
Urea and methylamines have similar effects on aldose reductase activity
Burg, M. B., & Peters, E. M. (1997) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.1997.273.6.f1048 · Cited by 20 · see citing works
The Effect of Polyethylene Glycol on the Mechanics and ATPase Activity of Active Muscle Fibers
Chinn, M. K., Myburgh, K. H., Pham, T., Franks-Skiba, K. E., & Cooke, R. (2000) · Biophysical Journal · doi:10.1016/s0006-3495(00)76650-1 · Cited by 16 · see citing works
West, T. G., Ferenczi, M. A., WOLEDGE, R. C., & Curtin, N. A. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.087106 · Cited by 14 · see citing works
Kumemoto, R., Hosogoe, Y., Nomura, N., & Hatori, K. (2011) · The Journal of Biochemistry · doi:10.1093/jb/mvr020 · Cited by 7 · see citing works
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Witkowski, M., Weeks, T. L., & Hazen, S. L. (2020) · Circulation Research · doi:10.1161/circresaha.120.316242 · Cited by 1,051 · see citing works
Trøseid, M., Ueland, T., Hov, J. R., Svardal, A., Gregersen, I., Dahl, C. P., Aakhus, S., Gude, E., Bjørndal, B., Halvorsen, B., et al. (2015) · Journal of Internal Medicine · doi:10.1111/joim.12328 · Cited by 464 · see citing works
Marine fish may be biochemically constrained from inhabiting the deepest ocean depths
Yancey, P. H., Gerringer, M. E., Drazen, J. C., Rowden, A. A., & Jamieson, A. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1322003111 · Cited by 284 · see citing works
Trimethylamine- N -Oxide: Friend, Foe, or Simply Caught in the Cross-Fire?
Cho, C. E., & Caudill, M. A. (2016) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2016.10.005 · Cited by 218 · see citing works
Yancey, P. H., & Siebenaller, J. F. (2015) · Journal of Experimental Biology · doi:10.1242/jeb.114355 · Cited by 155 · see citing works
Li, W., Huang, A., Zhu, H., Liu, X., Huang, X., Huang, Y., Cai, X., Lu, J., & Huang, Y. (2020) · The Medical Journal of Australia · doi:10.5694/mja2.50781 · Cited by 95 · see citing works
Yao, M., Liao, P., Zhao, X., & Wang, L. (2020) · BMC Cardiovascular Disorders · doi:10.1186/s12872-019-01310-5 · Cited by 89 · see citing works
Ufnal, M., & Nowiński, A. (2019) · Medical Hypotheses · doi:10.1016/j.mehy.2019.109271 · Cited by 41 · see citing works
Gut Microbiome Alterations in Patients With Carotid Atherosclerosis
Chen, J., Qin, Q., Su, Y., Yang, Y., Yan, H., Li, T., Wang, L., Gao, X., Li, A., & Ding, S. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.739093 · Cited by 42 · see citing works
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Kalantari, S., & Nafar, M. (2019) · Biomarkers in Medicine · doi:10.2217/bmm-2019-0008 · Cited by 31 · see citing works
yuzefpolskaya, M., Bohn, B., Javaid, A., Mondellini, G. M., Braghieri, L., Pinsino, A., Onat, D., Cagliostro, B., Kim, A. D., Takeda, K., et al. (2021) · Circulation Heart Failure · doi:10.1161/circheartfailure.120.007909 · Cited by 25 · see citing works
Wild, E., Bonifas, U., Klimek, J., Trösemeier, J., Krämer, B., Kegel, B., & Behrensdorf-Nicol, H. A. (2016) · Toxicology in Vitro · doi:10.1016/j.tiv.2016.03.011 · Cited by 23 · see citing works
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Hatori, K., Iwasaki, T., & Wada, R. (2014) · Biophysical Chemistry · doi:10.1016/j.bpc.2014.07.001 · Cited by 22 · see citing works
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Arns, L., Schuabb, V., Meichsner, S. L., Berghaus, M., & Winter, R. (2017) · Zeitschrift für Physikalische Chemie · doi:10.1515/zpch-2017-1039 · Cited by 12 · see citing works
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Wen, Y., Zhang, X., & Larsson, L. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.849973 · Cited by 7 · see citing works
Munmun, T., Kabir, A. M. R., Sada, K., & Kakugo, A. (2019) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2019.127231 · Cited by 5 · see citing works
Coughlin, D. J., Long, G. M., Gezzi, N. L., Modi, P. M., & Woluko, K. N. (2016) · Journal of Experimental Biology · doi:10.1242/jeb.135269 · Cited by 4 · see citing works
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Kottarathil, A., Rajkumar, D. S., & Rajashree, P. (2023) · Journal of Liquid Chromatography & Related Technologies · doi:10.1080/10826076.2023.2284737 · Cited by 3 · see citing works
Wada, R., Sato, D., Nakamura, T., & Hatori, K. (2015) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2015.10.001 · Cited by 3 · see citing works
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- Authors
- Kumemoto, R., Yusa, K., Shibayama, T., & Hatori, K.
- Affiliations
- Yamagata University (JP)
- Corresponding author
- Hatori, Kuniyuki
- ORCID
- Hatori, Kuniyuki
- Venue
- Biochimica et Biophysica Acta (BBA) - General Subjects
- Publisher
- Elsevier BV
- Published
- 2012-10
- Volume
- 1820
- Issue
- 10
- Pages
- 1597-1604
- ISSN
- 0304-4165 (ISSN-L)
- OpenAlex
- W2020783341
- Cited by
- 31
- References
- 31
- Citations by year
- 2026: 1 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 1
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochimica et Biophysica Acta (BBA) - General Subjects (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Keywords
- trimethylamine N-oxide, actomyosin motor, heavy meromyosin, ATPase activity, sliding velocity, protein hydration, hydrogen bonding, urea, osmolytes, actin filament motility, protein stability
- MeSH terms
- Actomyosin, Adenosine Triphosphatases, Animals, Dose-Response Relationship, Drug, Methylamines, Actin Cytoskeleton, Movement, Osmolar Concentration, Rabbits, Urea, Down-Regulation, Myosin Subfragments, Multiprotein Complexes, Protein Stability, In Vitro Techniques
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