Analyze Diet
Molecules (Basel, Switzerland)2018; 23(2); 287; doi: 10.3390/molecules23020287

The Effect of Methyl-β-cyclodextrin on Apoptosis, Proliferative Activity, and Oxidative Stress in Adipose-Derived Mesenchymal Stromal Cells of Horses Suffering from Metabolic Syndrome (EMS).

Abstract: Methyl-β-cyclodextrin (MβCD) is a cyclic oligosaccharide, commonly used as a pharmacological agent to deplete membrane cholesterol. In this study, we examined the effect of MβCD on adipose-derived mesenchymal stromal cells (ASCs) isolated form healthy horses (ASC) and from horses suffering from metabolic syndrome (ASC). We investigated the changes in the mRNA levels of the glucose transporter 4 (GLUT4) and found that MβCD application may lead to a significant improvement in glucose transport in ASC. We also showed that MβCD treatment affected GLUT4 upregulation in an insulin-independent manner via an NO-dependent signaling pathway. Furthermore, the analysis of superoxide dismutase activity (SOD) and reactive oxygen species (ROS) levels showed that MβCD treatment was associated with an increased antioxidant capacity in ASC. Moreover, we indicated that methyl-β-cyclodextrin treatment did not cause a dysfunction of the endoplasmic reticulum and lysosomes. Thereby, we propose the possibility of improving the functionality of ASC by increasing their metabolic stability.
Publication Date: 2018-01-30 PubMed ID: 29385746PubMed Central: PMC6017619DOI: 10.3390/molecules23020287Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research study investigates the impact of methyl-β-cyclodextrin (MβCD), a drug used to reduce cholesterol, on the health and function of adipose-derived mesenchymal stromal cells (ASCs) in horses, particularly those suffering from metabolic syndrome. The study provides optimism by suggesting MβCD treatment may improve glucose transport in ASCs, enhance antioxidant capacity, and improve metabolic stability without damaging specific cell structures.

Overview of the Research

  • The purpose of this study is to understand the influence of methyl-β-cyclodextrin (MβCD) on adipose-derived mesenchymal stromal cells (ASCs) in horses, especially those with metabolic syndrome.
  • MβCD is a cyclic oligosaccharide and is widely used as a pharmacological agent to remove cholesterol from cell membranes.
  • The researchers were interested in how MβCD affects the health and performance of ASCs in horses.

Effect on Glucose Transporter 4

  • The study particularly investigates the impact on glucose transporter 4 (GLUT4), a protein involved in the movement of glucose across cell membranes.
  • The researchers found that treatment with MβCD potentially improves the transportation of glucose in the ASCs, contributing to cell health and function.
  • Fascinatingly, this GLUT4 upregulation occurs in an insulin-independent manner, which means that MβCD treatment affects GLUT4 activity regardless of the presence or absence of insulin.
  • This GLUT4 upregulation is achieved through an NO-dependent signaling pathway, involving Nitric Oxide, a potent vasodilator.

Antioxidant Capacity and Cell Dysfunction

  • The researchers also evaluated superoxide dismutase activity (SOD) and reactive oxygen species (ROS) levels associated with antioxidant activity.
  • Increased SOD activity and ROS levels indicated that MβCD treatment is linked to higher antioxidant capacity in ASCs, improving the ability to protect against oxidative stress.
  • Along with the effect on GLUT4 and antioxidant capacity, researchers found no evidence that MβCD treatment would cause disruption to the endoplasmic reticulum and lysosomes—critical components of cell function.

Implications of the Study

  • The study hence suggests that the use of MβCD could lead to improved functionality of ASCs, especially by enhancing their metabolic stability.
  • Although the research is focused on horses, findings related to cellular function and the effects of MβCD may transfer across species, providing insights for human medicine as well.

Cite This Article

APA
Szydlarska J, Weiss C, Marycz K. (2018). The Effect of Methyl-β-cyclodextrin on Apoptosis, Proliferative Activity, and Oxidative Stress in Adipose-Derived Mesenchymal Stromal Cells of Horses Suffering from Metabolic Syndrome (EMS). Molecules, 23(2), 287. https://doi.org/10.3390/molecules23020287

Publication

ISSN: 1420-3049
NlmUniqueID: 100964009
Country: Switzerland
Language: English
Volume: 23
Issue: 2
PII: 287

Researcher Affiliations

Szydlarska, Joanna
  • Department of Experimental Biology and Electron Microscope Facility, The Faculty of Biology and Animal Science, Wroclaw University of Environmental and Life Sciences, 50-631 Wroclaw, Poland. joanna.szydlarska@gmail.com.
Weiss, Christine
  • Department of Experimental Biology and Electron Microscope Facility, The Faculty of Biology and Animal Science, Wroclaw University of Environmental and Life Sciences, 50-631 Wroclaw, Poland. d.weiss@horsedoc.ch.
Marycz, Krzysztof
  • Department of Experimental Biology and Electron Microscope Facility, The Faculty of Biology and Animal Science, Wroclaw University of Environmental and Life Sciences, 50-631 Wroclaw, Poland. krzysztofmarycz@interia.pl.
  • Wroclaw Research Centre EIT+, 54-066 Wroclaw, Poland. krzysztofmarycz@interia.pl.

MeSH Terms

  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • Animals
  • Cell Proliferation / drug effects
  • Horse Diseases / metabolism
  • Horse Diseases / pathology
  • Horses
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / pathology
  • Metabolic Syndrome / metabolism
  • Metabolic Syndrome / pathology
  • Metabolic Syndrome / veterinary
  • Oxidative Stress / drug effects
  • beta-Cyclodextrins / pharmacology

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 45 references
  1. Giles SL, Rands SA, Nicol CJ, Harris PA. Obesity prevalence and associated risk factors in outdoor living domestic horses and ponies.. PeerJ 2014;2:e299.
    doi: 10.7717/peerj.299pmc: PMC3970797pubmed: 24711963google scholar: lookup
  2. Ertelt A, Barton AK, Schmitz RR, Gehlen H. Metabolic syndrome: is equine disease comparable to what we know in humans?. Endocr Connect 2014 Sep;3(3):R81-93.
    doi: 10.1530/EC-14-0038pmc: PMC4068110pubmed: 24894908google scholar: lookup
  3. Marycz K, Kornicka K, Basinska K, Czyrek A. Equine Metabolic Syndrome Affects Viability, Senescence, and Stress Factors of Equine Adipose-Derived Mesenchymal Stromal Stem Cells: New Insight into EqASCs Isolated from EMS Horses in the Context of Their Aging.. Oxid Med Cell Longev 2016;2016:4710326.
    doi: 10.1155/2016/4710326pmc: PMC4670679pubmed: 26682006google scholar: lookup
  4. Marędziak M, Marycz K, Lewandowski D, Siudzińska A, Śmieszek A. Static magnetic field enhances synthesis and secretion of membrane-derived microvesicles (MVs) rich in VEGF and BMP-2 in equine adipose-derived stromal cells (EqASCs)-a new approach in veterinary regenerative medicine.. In Vitro Cell Dev Biol Anim 2015 Mar;51(3):230-40.
    doi: 10.1007/s11626-014-9828-0pmc: PMC4368852pubmed: 25428200google scholar: lookup
  5. Matsushita K. Mesenchymal Stem Cells and Metabolic Syndrome: Current Understanding and Potential Clinical Implications.. Stem Cells Int 2016;2016:2892840.
    doi: 10.1155/2016/2892840pmc: PMC4903149pubmed: 27313625google scholar: lookup
  6. Baraniak PR, McDevitt TC. Stem cell paracrine actions and tissue regeneration.. Regen Med 2010 Jan;5(1):121-43.
    doi: 10.2217/rme.09.74pmc: PMC2833273pubmed: 20017699google scholar: lookup
  7. Basinska K, Marycz K, Śieszek A, Nicpoń J. The production and distribution of IL-6 and TNF-a in subcutaneous adipose tissue and their correlation with serum concentrations in Welsh ponies with equine metabolic syndrome.. J Vet Sci 2015;16(1):113-20.
    doi: 10.4142/jvs.2015.16.1.113pmc: PMC4367141pubmed: 25269712google scholar: lookup
  8. Wei X, Yang X, Han ZP, Qu FF, Shao L, Shi YF. Mesenchymal stem cells: a new trend for cell therapy.. Acta Pharmacol Sin 2013 Jun;34(6):747-54.
    doi: 10.1038/aps.2013.50pmc: PMC4002895pubmed: 23736003google scholar: lookup
  9. Marycz K, Kornicka K, Marędziak M, Golonka P, Nicpoń J. Equine metabolic syndrome impairs adipose stem cells osteogenic differentiation by predominance of autophagy over selective mitophagy.. J Cell Mol Med 2016 Dec;20(12):2384-2404.
    doi: 10.1111/jcmm.12932pmc: PMC5134411pubmed: 27629697google scholar: lookup
  10. Marycz K, Kornicka K, Grzesiak J, Śmieszek A, Szłapka J. Macroautophagy and Selective Mitophagy Ameliorate Chondrogenic Differentiation Potential in Adipose Stem Cells of Equine Metabolic Syndrome: New Findings in the Field of Progenitor Cells Differentiation.. Oxid Med Cell Longev 2016;2016:3718468.
    doi: 10.1155/2016/3718468pmc: PMC5178365pubmed: 28053691google scholar: lookup
  11. Gylling H, Hallikainen M, Pihlajamäki J, Simonen P, Kuusisto J, Laakso M, Miettinen TA. Insulin sensitivity regulates cholesterol metabolism to a greater extent than obesity: lessons from the METSIM Study.. J Lipid Res 2010 Aug;51(8):2422-7.
    doi: 10.1194/jlr.P006619pmc: PMC2903787pubmed: 20436182google scholar: lookup
  12. Ikonen E. Mechanisms for cellular cholesterol transport: defects and human disease.. Physiol Rev 2006 Oct;86(4):1237-61.
    doi: 10.1152/physrev.00022.2005pubmed: 17015489google scholar: lookup
  13. Goluszko P, Nowicki B. Membrane cholesterol: a crucial molecule affecting interactions of microbial pathogens with mammalian cells.. Infect Immun 2005 Dec;73(12):7791-6.
  14. Diaz-Arjonilla M, Schwarcz M, Swerdloff RS, Wang C. Obesity, low testosterone levels and erectile dysfunction.. Int J Impot Res 2009 Mar-Apr;21(2):89-98.
    doi: 10.1038/ijir.2008.42pubmed: 18843273google scholar: lookup
  15. Grantham JP, Henneberg M. The estrogen hypothesis of obesity.. PLoS One 2014;9(6):e99776.
  16. Das A, Brown MS, Anderson DD, Goldstein JL, Radhakrishnan A. Three pools of plasma membrane cholesterol and their relation to cholesterol homeostasis.. Elife 2014 Jun 11;3.
    doi: 10.7554/eLife.02882pmc: PMC4086274pubmed: 24920391google scholar: lookup
  17. Llanos P, Contreras-Ferrat A, Georgiev T, Osorio-Fuentealba C, Espinosa A, Hidalgo J, Hidalgo C, Jaimovich E. The cholesterol-lowering agent methyl-β-cyclodextrin promotes glucose uptake via GLUT4 in adult muscle fibers and reduces insulin resistance in obese mice.. Am J Physiol Endocrinol Metab 2015 Feb 15;308(4):E294-305.
    doi: 10.1152/ajpendo.00189.2014pubmed: 25491723google scholar: lookup
  18. Le Lay S, Krief S, Farnier C, Lefrère I, Le Liepvre X, Bazin R, Ferré P, Dugail I. Cholesterol, a cell size-dependent signal that regulates glucose metabolism and gene expression in adipocytes.. J Biol Chem 2001 May 18;276(20):16904-10.
    doi: 10.1074/jbc.M010955200pubmed: 11278795google scholar: lookup
  19. Chang L, Chiang SH, Saltiel AR. Insulin signaling and the regulation of glucose transport.. Mol Med 2004 Jul-Dec;10(7-12):65-71.
    doi: 10.2119/2005-00029.Saltielpmc: PMC1431367pubmed: 16307172google scholar: lookup
  20. Antonescu CN, Foti M, Sauvonnet N, Klip A. Ready, set, internalize: mechanisms and regulation of GLUT4 endocytosis.. Biosci Rep 2009 Feb;29(1):1-11.
    doi: 10.1042/BSR20080105pubmed: 19143591google scholar: lookup
  21. Karlsson M, Thorn H, Parpal S, Strålfors P, Gustavsson J. Insulin induces translocation of glucose transporter GLUT4 to plasma membrane caveolae in adipocytes.. FASEB J 2002 Feb;16(2):249-51.
    doi: 10.1096/fj.01-0646fjepubmed: 11744627google scholar: lookup
  22. Barnes K, Ingram JC, Bennett MD, Stewart GW, Baldwin SA. Methyl-beta-cyclodextrin stimulates glucose uptake in Clone 9 cells: a possible role for lipid rafts.. Biochem J 2004 Mar 1;378(Pt 2):343-51.
    doi: 10.1042/bj20031186pmc: PMC1223971pubmed: 14616090google scholar: lookup
  23. Hallikainen M, Toppinen L, Mykkänen H, Agren JJ, Laaksonen DE, Miettinen TA, Niskanen L, Poutanen KS, Gylling H. Interaction between cholesterol and glucose metabolism during dietary carbohydrate modification in subjects with the metabolic syndrome.. Am J Clin Nutr 2006 Dec;84(6):1385-92.
    pubmed: 17158421doi: 10.1093/ajcn/84.6.1385google scholar: lookup
  24. Zidovetzki R, Levitan I. Use of cyclodextrins to manipulate plasma membrane cholesterol content: evidence, misconceptions and control strategies.. Biochim Biophys Acta 2007 Jun;1768(6):1311-24.
  25. Christian AE, Haynes MP, Phillips MC, Rothblat GH. Use of cyclodextrins for manipulating cellular cholesterol content.. J Lipid Res 1997 Nov;38(11):2264-72.
    pubmed: 9392424
  26. Hao M, Head WS, Gunawardana SC, Hasty AH, Piston DW. Direct effect of cholesterol on insulin secretion: a novel mechanism for pancreatic beta-cell dysfunction.. Diabetes 2007 Sep;56(9):2328-38.
    doi: 10.2337/db07-0056pubmed: 17575085google scholar: lookup
  27. Habegger KM, Hoffman NJ, Ridenour CM, Brozinick JT, Elmendorf JS. AMPK enhances insulin-stimulated GLUT4 regulation via lowering membrane cholesterol.. Endocrinology 2012 May;153(5):2130-41.
    doi: 10.1210/en.2011-2099pmc: PMC3339638pubmed: 22434076google scholar: lookup
  28. Portilho DM, Soares CP, Morrot A, Thiago LS, Butler-Browne G, Savino W, Costa ML, Mermelstein C. Cholesterol depletion by methyl-β-cyclodextrin enhances cell proliferation and increases the number of desmin-positive cells in myoblast cultures.. Eur J Pharmacol 2012 Nov 5;694(1-3):1-12.
    doi: 10.1016/j.ejphar.2012.07.035pubmed: 22921450google scholar: lookup
  29. Choi YA, Chin BR, Rhee DH, Choi HG, Chang HW, Kim JH, Baek SH. Methyl-beta-cyclodextrin inhibits cell growth and cell cycle arrest via a prostaglandin E(2) independent pathway.. Exp Mol Med 2004 Feb 29;36(1):78-84.
    doi: 10.1038/emm.2004.11pubmed: 15031675google scholar: lookup
  30. Hailstones D, Sleer LS, Parton RG, Stanley KK. Regulation of caveolin and caveolae by cholesterol in MDCK cells.. J Lipid Res 1998 Feb;39(2):369-79.
    pubmed: 9507997
  31. Mahavadi S, Nalli A, Kumar D, Bhattacharya S, Zhou R, Grider J, Murthy K. Increased expression of caveolin-1 is associated with upregulation of the RhoA/Rho kinase pathway and smooth muscle contraction in diabetes (1110.11). FASEB J 2014;28.
  32. Garofalo T, Matarrese P, Manganelli V, Marconi M, Tinari A, Gambardella L, Faggioni A, Misasi R, Sorice M, Malorni W. Evidence for the involvement of lipid rafts localized at the ER-mitochondria associated membranes in autophagosome formation.. Autophagy 2016 Jun 2;12(6):917-35.
  33. Kameyama K, Motoyama K, Tanaka N, Yamashita Y, Higashi T, Arima H. Induction of mitophagy-mediated antitumor activity with folate-appended methyl-β-cyclodextrin.. Int J Nanomedicine 2017;12:3433-3446.
    doi: 10.2147/IJN.S133482pmc: PMC5417668pubmed: 28496320google scholar: lookup
  34. Sarkar S, Carroll B, Buganim Y, Maetzel D, Ng AH, Cassady JP, Cohen MA, Chakraborty S, Wang H, Spooner E, Ploegh H, Gsponer J, Korolchuk VI, Jaenisch R. Impaired autophagy in the lipid-storage disorder Niemann-Pick type C1 disease.. Cell Rep 2013 Dec 12;5(5):1302-15.
  35. Huang S, Czech MP. The GLUT4 glucose transporter.. Cell Metab 2007 Apr;5(4):237-52.
    doi: 10.1016/j.cmet.2007.03.006pubmed: 17403369google scholar: lookup
  36. Al-Makdissy N, Younsi M, Pierre S, Ziegler O, Donner M. Sphingomyelin/cholesterol ratio: an important determinant of glucose transport mediated by GLUT-1 in 3T3-L1 preadipocytes.. Cell Signal 2003 Nov;15(11):1019-30.
    doi: 10.1016/S0898-6568(03)00070-6pubmed: 14499345google scholar: lookup
  37. Rudrappa BG, Aski BS, Kashinath RT. Effect of Membrane Cholesterol on Glucose Uptake in Diabetic Erythrocytes. Glob. J. Med. Res. 2012;12:18–22.
  38. Merry TL, McConell GK. Skeletal muscle glucose uptake during exercise: a focus on reactive oxygen species and nitric oxide signaling.. IUBMB Life 2009 May;61(5):479-84.
    doi: 10.1002/iub.179pubmed: 19391163google scholar: lookup
  39. Tanaka S, Yashiro A, Nakashima Y, Nanri H, Ikeda M, Kuroiwa A. Plasma nitrite/nitrate level is inversely correlated with plasma low-density lipoprotein cholesterol level.. Clin Cardiol 1997 Apr;20(4):361-5.
    doi: 10.1002/clc.4960200412pmc: PMC6655312pubmed: 9098596google scholar: lookup
  40. Gheibi S, Bakhtiarzadeh F, Jeddi S, Farrokhfall K, Zardooz H, Ghasemi A. Nitrite increases glucose-stimulated insulin secretion and islet insulin content in obese type 2 diabetic male rats.. Nitric Oxide 2017 Apr 1;64:39-51.
    doi: 10.1016/j.niox.2017.01.003pubmed: 28089828google scholar: lookup
  41. Tanaka T, Nakatani K, Morioka K, Urakawa H, Maruyama N, Kitagawa N, Katsuki A, Araki-Sasaki R, Hori Y, Gabazza EC, Yano Y, Wada H, Nobori T, Sumida Y, Adachi Y. Nitric oxide stimulates glucose transport through insulin-independent GLUT4 translocation in 3T3-L1 adipocytes.. Eur J Endocrinol 2003 Jul;149(1):61-7.
    doi: 10.1530/eje.0.1490061pubmed: 12824867google scholar: lookup
  42. Cavener DR, Gupta S, McGrath BC. PERK in beta cell biology and insulin biogenesis.. Trends Endocrinol Metab 2010 Dec;21(12):714-21.
    doi: 10.1016/j.tem.2010.08.005pmc: PMC2991375pubmed: 20850340google scholar: lookup
  43. Ballabio A, Gieselmann V. Lysosomal disorders: from storage to cellular damage.. Biochim Biophys Acta 2009 Apr;1793(4):684-96.
    doi: 10.1016/j.bbamcr.2008.12.001pubmed: 19111581google scholar: lookup
  44. Doubling Time Online Computing with 2 Points. [(accessed on 9 October 2017)]; Available online: http://www.doubling-time.com/compute.php.
  45. Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.. Anal Biochem 1987 Apr;162(1):156-9.
    doi: 10.1016/0003-2697(87)90021-2pubmed: 2440339google scholar: lookup

Citations

This article has been cited 1 times.
  1. Ferreira-Baptista C, Queirós A, Ferreira R, Fernandes MH, Colaço B, Gomes PS. The Osteogenic Potential of Falciform Ligament-Derived Stromal Cells-A Comparative Analysis between Two Osteogenic Induction Programs.. Bioengineering (Basel) 2022 Dec 15;9(12).
    doi: 10.3390/bioengineering9120810pubmed: 36551016google scholar: lookup