Abstract
The biological membranes are important in cell function but, during development of diseases such as diabetes, they are impaired. Consequently, membrane-associated biological processes are impaired as well. The mitochondria are important organelles where oxidative phosphorylation takes place, a process closely related with the membranes. In general, it is accepted that the development process of diabetes decreases membrane fluidity. However, in some cases, it has been found to increase membrane fluidity of mitochondria but to decrease the Respiratory Control (RC) index. In this study we found an increase of membrane fluidity and an increase of the RC at an early phase of the development of a type 2 diabetes model. We measured the lipoperoxidation, analyzed the fatty acids composition by gas chromatography, and assessed membrane fluidity using three fluorescent monitors located at different depths inside the bilayer, dipyrenilpropane (DPyP), diphenylhexatriene (DPH), and trimethylammonium diphenylhexatriene (TMA-DPH). Our findings indicate that in the initial stage of diabetes development, when lipoperoxidation still is not significant, the membrane fluidity of liver mitochondria increases because of the increment in the unsaturated to saturated fatty acids ratio (U/S), thus producing an increase of the RC. The membrane fluidity is not the same at all depths in the bilayer. Contrary to the results obtained in mitochondria, the diabetes induced a decrease in the U/S fatty acids ratio of liver total lipids, indicating that the mitochondria might have an independent mechanism for regulating its fatty acids composition.
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Almeida LM, Vaz WL, Zachariasse KA, Madeira VM (1982) Fluidity of sarcoplasmic reticulum membranes investigated with dipyrenylpropane, an intramolecular excimer probe. Biochemistry 21:5972–5977
Ames GF (1968) Lipids of Salmonella typhimurium and Escherichia coli: structure and metabolism. J Bacteriol 95:833–843
Bligh E, Dyer W (1959) A rapid method of total lipid extraction and purification. Can J Biochem Phys 37:911–917
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254
Costa J, Borges M, David C, Vaz Carneiro A (2006) Efficacy of lipid lowering drug treatment for diabetic and non-diabetic patients: meta-analysis of randomized controlled trials. BMJ 332(7550):1115–1124. doi:10.1136/bmj.38793.468449.AE
Damasceno DC, Sinzato YK, Bueno A, Netto AO, Dallaqua B, Gallego FQ, Iessi IL, Corvino SB, Serrano RG, Marini G, Piculo F, Calderon IMP, Rudge F (2013) Mild diabetes models and their maternal-fetal repercussions 2013:473575. doi:10.1155/2013/473575
Dey A, Swaminathan K (2010) Hyperglycemia-induced mitochondrial alterations in liver. Life Sci 87(7–8):197–214. doi:10.1016/j.lfs.2010.06.007
Fagone P, Jackowski S (2009) Membrane phospholipid synthesis and endoplasmic reticulum function. J Lipid Res 50(Suppl):S311–S316. doi:10.1194/jlr.R800049-JLR200
Figueroa-García MC, Espinosa-García MT, Martínez-Montes F, Palomar-Morales M, Mejía-Zepeda R (2015) Even a chronic mild hyperglycemia affects membrane fluidity and lipoperoxidation in placental mitocondria in Wistar rats. PLoS One 10(12):1–15. doi:10.1371/journal.pone.0143778
Folch J, Lees M, Sloane-Stanley GH (1957) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226:497–509
Hall ED, Wang JA, Bosken JM, Singh IN (2016) Lipid peroxidation in brain or spinal cord mitochondria after injury. J Bioenerg Biomembr 48(2):169–174. doi:10.1007/s10863-015-9600-5
IDF Diabetes Atlas (2015) International Diabetes Federation, 7th edn
van Meer G, Voelker DR, Feigenson GW (2008) Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol 9(2):112–124. doi:10.1038/nrm2330
Mejia EM, Hatch GM (2016) Mitochondrial phospholipids: role in mitochondrial function. J Bioenerg Biomembr 48(2):99–112. doi:10.1007/s10863-015-9601-4
Morrison WR, Smith LM (1964) Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride-methanol. J Lipid Res 5:600–608
Nanetti L, Vignini A, Raffaelli F, Moroni C, Silvestrini M, Provinciali L, Mazanti L (2008) Platelet membrane fluidity and Na+/K+ ATPase activity in acute stroke. Brain Res 1205:21–26. doi:10.1016/j.brainres.2008.02.005
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358
Patil MA, Suryanarayana P, Putcha UK, Srinivas M, Reddy GB (2014) Evaluation of neonatal streptozotocin induced diabetic rat model for the development of cataract. Oxidative Med Cell Longev 2014:463264. doi:10.1155/2014/463264
Patwardham GA, Beverly LJ, Siskind LJ (2016) Sphingolipids and mitochondrial apoptosis. J Bioenerg Biomembr 48(2):153–168. doi:10.1007/s10863-015-9602-3
Pérez-Hernández IH, Avendaño-Flores YS, Mejía-Zepeda R (2010) Analysis of the membrane fluidity of erythrocyte ghosts in diabetic, spontaneously hypertensive rats. Acta Diabetol 47(Suppl 1):S47–S55. doi:10.1007/s00592-009-0120-9
Pilon M (2016) Revisiting the membrane-centric view of diabetes. Lipids Health Dis 15(1):167. doi:10.1186/s12944-016-0342-0
Portha B, Picon L, Rosselin G (1979) Chemical diabetes in the adult rat as the spontaneous evolution of neonatal diabetes. Diabetologia 17:371–377
Raza H, Prabu SK, John A, Avadhani NG (2011) Impaired mitochondrial respiratory functions and oxidative stress in streptozotocin-induced diabetic rats. Int J Mol Sci 12(5):3133–3147. doi:10.3390/ijms12053133
Robertson RP, Harmon JS (2006) Diabetes, glucose toxicity, and oxidative stress: a case of double jeopardy for the pancreatic islet β cell. Free Radic Biol Med 41(2):177–184. doi:10.1016/j.freeradbiomed.2005.04.030
Rolo AP, Palmeira CM (2006) Diabetes and mitocondrial function: role of hyperglycemia and oxidative stress. Toxicol Appl Pharmacol 212:167–178. doi:10.1016/j.taap.2006.01.003
Rossy J, Ma Y, Gaus K (2014) The organisation of the cell membrane: do proteins rule lipids? Curr Opin Chem Biol 20:54–59. doi:10.1016/jcbpa.2014.04.009
Santos DL, Palmeira CM, Seiça R, Dias J, Mesquita J, Moreno AJ, Santos MS (2003) Diabetes and mitocondrial oxidative stress: a study using heart mitochondria from the diabetic Goto-Kakizaki rat. Mol Cell Biochem 246(1–2):163–170
Shivaji S, Prakash JSS (2010) How do bacteria sense and respond to low temperature? Arch Microbiol 192:85–95. doi:10.1007/s00203-009-0539-y
Vergeade A, Bertram CC, Bikineyeva AT, Zackert WE, Zinkel SS, May JM, Dikalov SI, Roberts LJ, Boutaud O (2016) Cardiolipin fatty acid remodeling regulates mitochondrial function by modifying the electron entry point in the respiratory chain. Mitochondrion 28:88–95. doi:10.1016/j.mito.2016.04.002
Waczulikova I, Habodaszova D, Cagalinec M, Ferko M, Ulicna O, Mateasik A, Sikurova L, Ziegelhöffer A (2007) Mitochondrial membrane fluidity, potential, and calcium transients in the myocardium from acute diabetic rats. Can J Physiol Pharmacol 85:372–381. doi:10.1139/Y07-035
Wang RN, Bouwens L, Klöppel G (1994) Beta-cell proliferation in normal and streptozotocin-treated newborn rats: site, dynamics and capacity. Diabetologia 37:1088–1096
Weijers RNM (2012) Lipid composition of cell membranes and its relevance in type 2 diabetes mellitus. Curr Diabetes Rev 8:390–400
Acknowledgements
We thank the financial support for this project from Programa de Apoyo a Proyectos de Investigación a Innovación Tecnológica PAPIIT IN-216314 to RMZ- Dirección General de Asuntos del Personal Académico de la Universidad Nacional Autónoma de México (DGAPA-UNAM). We also thank to the Posgrado en Ciencias Biológicas-UNAM and the Consejo Nacional de Ciencia y Tecnología (CONACYT) for the fellowship 233851 to IHPH.
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Pérez-Hernández, I.H., Domínguez-Fuentes, J.M., Palomar-Morales, M. et al. Liver mitochondrial membrane fluidity at early development of diabetes and its correlation with the respiration. J Bioenerg Biomembr 49, 231–239 (2017). https://doi.org/10.1007/s10863-017-9700-5
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DOI: https://doi.org/10.1007/s10863-017-9700-5