COMPREHENSIVE MOLECULAR STUDY REVEALS THE POTENTIAL ROLE OF CHEBULINIC ACID AND BOERAVINONE B TO ESTABLISH REDOX HOMEOSTASIS IN METABOLICALLY STRESSED CELLS

HARSHAD K. BOTE; SAMIDHA S. KAKADE; SHIVTEJ P. BIRADAR; RAHUL V. KHANDARE; PANKAJ K. PAWAR

doi:10.22159/ijpps.2022v14i7.45042

Authors

HARSHAD K. BOTE Department of Biochemistry, Shivaji University, Kolhapur 416004, India https://orcid.org/0000-0002-7362-635X
SAMIDHA S. KAKADE Department of Biochemistry, Shivaji University, Kolhapur 416004, India https://orcid.org/0000-0001-7668-6705
SHIVTEJ P. BIRADAR Department of Biochemistry, Shivaji University, Kolhapur 416004, India
RAHUL V. KHANDARE Amity Institute of Biotechnology, Amity University, Mumbai, India https://orcid.org/0000-0003-0116-9847
PANKAJ K. PAWAR Department of Biochemistry, Shivaji University, Kolhapur 416004, India https://orcid.org/0000-0001-7668-6705

DOI:

https://doi.org/10.22159/ijpps.2022v14i7.45042

Keywords:

Redox homeostasis, Stress signaling, Mitochondrial membrane potential, Mitochondrial damage control, Apoptosis

Abstract

Objective: Our objective was to assess the multi-dimensional protective mechanism of Chebulinic acid (CA) and Boeravinone B (BB) against MG-induced metabolic stress and cytotoxicity.

Methods: In this study, we have studied CA-and BB-mediated changes in molecular markers of highly dynamic mechanisms of mitochondrial disintegration, nuclear damage and cell death pathways associated with early ageing in MG-exposed Saccharomyces cerevisiae cells using biochemical assays, qRT-PCR and flow cytometry.

Results: We found that CA and BB interventions during MG-induced stress in S. cerevisiae reduce the rate of extracellular nitrite production, protein carbonyl content, lipid peroxidation and in addition, photo components positively modulate the expression patterns of genes involved in different cell death pathways. Furthermore, CA and BB treatments to MG-stressed cells reduced the number of cells in late apoptosis by 13.4% and 28.3%, respectively. On top of that, CA and BB supplementation during MG-stress restored mitochondrial membrane potential (ΔΨm) by 63.0% and 62.5%, respectively.

Conclusion: Based on the results of this study, it seems CA and BB phytotherapy protect against MG-induced cytotoxicity through their natural antioxidant properties by establishing redox homeostasis; thus, CA and BB defend the cell components from oxidative damage of different biomolecules and organelles, ultimately increase longevity.

Downloads

Download data is not yet available.

References

Christensen K, Doblhammer G, Rau R, Vaupel JW. Ageing populations: the challenges ahead. Lancet. 2009 Oct 3;374(9696):1196-208. doi: 10.1016/S0140-6736(09)61460-4, PMID 19801098.

Mejía Barajas JA, Montoya Perez R, Salgado Garciglia R, Aguilera Aguirre L, Cortes Rojo C, Mejía Zepeda R. Oxidative stress and antioxidant response in a thermotolerant yeast. Braz J Microbiol. 2017 Jan 3;48(2):326-32. doi: 10.1016/j.bjm.2016.11.005, PMID 28094115.

Papinutti L, Mouso N, Forchiassin F. Removal and degradation of the fungicide dye malachite green from aqueous solution using the system wheat bran-Fomes sclerodermeus. Enzyme Microb Technol. 2006 Aug 2;39(4):848-53. doi: 10.1016/j.enzmictec.2006.01.013.

Luo J, Mills K, le Cessie S, Noordam R, van Heemst D. Ageing, age-related diseases and oxidative stress: what to do next? Ageing Res Rev. 2020 Jan 1;57:100982. doi: 10.1016/j.arr.2019.100982, PMID 31733333.

Dhamgaye S, Devaux F, Manoharlal R, Vandeputte P, Shah AH, Singh A. In vitro effect of malachite green on Candida albicans involves multiple pathways and transcriptional regulators UPC2 and STP2. Antimicrob Agents Chemother. 2012;56(1):495-506. doi: 10.1128/AAC.00574-11, PMID 22006003.

Kirkwood TBL. Understanding the odd science of aging. Cell. 2005 Feb 25;120(4):437-47. doi: 10.1016/j.cell.2005.01.027, PMID 15734677.

Jones OR, Scheuerlein A, Salguero Gomez R, Camarda CG, Schaible R, Casper BB. Diversity of ageing across the tree of life. Nature. 2014 Jan 9;505(7482):169-73. doi: 10.1038/nature12789, PMID 24317695.

Ridout KK, Levandowski M, Ridout SJ, Gantz L, Goonan K, Palermo D. Early life adversity and telomere length: a meta-analysis. Mol Psychiatry. 2018;23(4):858-71. doi: 10.1038/mp.2017.26, PMID 28322278.

DeBalsi KL, Hoff KE, Copeland WC. Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases. Ageing Res Rev. 2017 Jan 1;33:89-104. doi: 10.1016/j.arr.2016.04.006, PMID 27143693.

Bilinski T. Oxygen toxicity and microbial evolution. Biosystems. 1991 Jan 1;24(4):305-12. doi: 10.1016/0303-2647(91)90049-q, PMID 1863719.

Soundarya PK, Nirmala P, Kumar AP. Effect of lutein in hypercholesterolemia induced oxidative stress in male Wistar rats. Int J Curr Pharm Res. 2015 Apr 10;7(2):97-100.

Divate NR, Chen GH, Divate RD, Ou BR, Chung YC. Metabolic engineering of Saccharomyces cerevisiae for improvement in stresses tolerance. Bioengineered. 2017 Sep 3;8(5):524-35. doi: 10.1080/21655979.2016.1257449, PMID 27937123.

Maurya H, Kumar T. Formulation, standardization, and evaluation of polyherbal dispersible tablet. Int J App Pharm. 2019 Jul 1;11(1):158-67. doi: 10.22159/ijap.2019v11i1.30113.

Gond SP, Sahu S, Rawat S, Rajendiran A, Singh A. Immunomodulatory natural product [review]. Asian J Pharm Clin Res. 2022 Mar 23;15(5):5-9.

Biradar SP, Tamboli AS, Khandare RV, Pawar PK. Chebulinic acid and Boeravinone B act as anti-aging and anti-apoptosis phyto-molecules during oxidative stress. Mitochondrion. 2019 May 1;46:236-46. doi: 10.1016/j.mito.2018.07.003, PMID 30026131.

Saji N, Francis N, Schwarz LJ, Blanchard CL, Santhakumar AB. The antioxidant and anti-inflammatory properties of rice bran phenolic extracts. Foods. 2020 Jun 24;9(6):829. doi: 10.3390/foods9060829, PMID 32599964.

Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov 1;193(1):265-75. doi: 10.1016/S0021-9258(19)52451-6, PMID 14907713.

Chaiyarit S, Thongboonkerd V. Comparative analyses of cell disruption methods for mitochondrial isolation in high-throughput proteomics study. Anal Biochem. 2009 Nov 15;394(2):249-58. doi: 10.1016/j.ab.2009.07.026, PMID 19622339.

Colombo G, Clerici M, Garavaglia ME, Giustarini D, Rossi R, Milzani A. A step-by-step protocol for assaying protein carbonylation in biological samples. J Chromatogr B Anal Technol Biomed Life Sci. 2016 Apr 15;1019:178-90. doi: 10.1016/j.jchromb.2015.11.052, PMID 26706659.

Wade CR, Jackson PG, Highton J, Van Rij AM. Lipid peroxidation and malondialdehyde in the synovial fluid and plasma of patients with rheumatoid arthritis. Clin Chim Acta. 1987 May 15;164(3):245-50. doi: 10.1016/0009-8981(87)90298-1, PMID 3594915.

Mohammad K, Dakik P, Medkour Y, McAuley M, Mitrofanova D, Titorenko VI. Yeast cells exposed to exogenous palmitoleic acid either adapt to stress and survive or commit to regulated liponecrosis and die. Oxid Med Cell Longev. 2018 Jan 31;2018:3074769. doi: 10.1155/2018/3074769, PMID 29636840.

Shen L, Li Y, Jiang L, Wang X. Response of Saccharomyces cerevisiae to the stimulation of lipopolysaccharide. PLOS One. 2014 Aug 8;9(8):e104428. doi: 10.1371/journal.pone.0104428, PMID 25105496.

Ludovico P, Sansonetty F, Corte Real M. Assessment of mitochondrial membrane potential in yeast cell populations by flow cytometry. Microbiology (Reading). 2001 Dec 1;147(12):3335-43. doi: 10.1099/00221287-147-12-3335, PMID 11739765.

Aerts S, Haesbroeck G, Ruwet C. Multivariate coefficients of variation: comparison and influence functions. Journal of Multivariate Analysis. 2015 Dec 1;142:183-98. doi: 10.1016/j.jmva.2015.08.006.

Ayer A, Gourlay CW, Dawes IW. Cellular redox homeostasis, reactive oxygen species and replicative ageing in Saccharomyces cerevisiae. FEMS Yeast Res. 2014 Feb 1;14(1):60-72. doi: 10.1111/1567-1364.12114, PMID 24164795.

Nakamura T, Lipton SA. Nitric oxide-dependent protein post-translational modifications impair mitochondrial function and metabolism to contribute to neurodegenerative diseases. Antioxid Redox Signal. 2020 Apr 20;32(12):817-33. doi: 10.1089/ars.2019.7916, PMID 31657228.

Akram F, Fuchs D, Daue M, Nijjar G, Ryan A, Benros ME. Association of plasma nitrite levels with obesity and metabolic syndrome in the Old Order Amish. Obes Sci Pract. 2018 Jun 20;4(5):468-76. doi: 10.1002/osp4.290, PMID 30338117.

Tungmunnithum D, Abid M, Elamrani A, Drouet S, Addi M, Hano C. Almond skin extracts and chlorogenic acid delay chronological aging and enhanced oxidative stress response in yeast. Life (Basel). 2020 May 28;10(6):80. doi: 10.3390/ life10060080, PMID 32481725.

Fussell JC, Kelly FJ. Oxidative contribution of air pollution to extrinsic skin ageing. Free Radic Biol Med. 2020 May 1;151:111-22. doi: 10.1016/j.freeradbiomed.2019.11.038, PMID 31874249.

Conrad M, Kagan VE, Bayir H, Pagnussat GC, Head B, Traber MG. Regulation of lipid peroxidation and ferroptosis in diverse species. Genes Dev. 2018 May 1;32(9-10):602-19. doi: 10.1101/gad.314674.118, PMID 29802123.

Barrera G, Pizzimenti S, Daga M, Dianzani C, Arcaro A, Cetrangolo GP. Lipid peroxidation-derived aldehydes, 4-hydroxynonenal and malondialdehyde in aging-related disorders. Antioxidants (Basel). 2018 Jul 30;7(8):102. doi: 10.3390/antiox7080102, PMID 30061536.

Jacquet M, Renault G, Lallet S, De Mey J, Goldbeter A. Oscillatory nucleocytoplasmic shuttling of the general stress response transcriptional activators Msn2 and Msn4 in saccharomyces cerevisiae. J Cell Biol. 2003 May 12;161(3):497-505. doi: 10.1083/jcb.200303030, PMID 12732613.

Brombacher K, Fischer BB, Rufenacht K, Eggen RI. The role of Yap1p and Skn7p-mediated oxidative stress response in defence of saccharomyces cerevisiae against singlet oxygen. Yeast. 2006 Jul 30;23(10):741-50. doi: 10.1002/yea.1392, PMID 16862604.

Hu Y, Cao JJ, Liu P, Guo DH, Wang YP, Yin J. Protective role of tea polyphenols in combination against radiation-induced hematopoietic and biochemical alterations in mice. Phytother Res. 2011 Mar 31;25(12):1761-9. doi: 10.1002/ptr.3483, PMID 21452375.

Kan J, Hu Y, Ge Y, Zhang W, Lu S, Zhao C. Declined expressions of vast mitochondria-related genes represented by CYCS and transcription factor ESRRA in skeletal muscle aging. Bioengineered. 2021 Jan 1;12(1):3485-502. doi: 10.1080/21655979.2021.1948951, PMID 34229541.

Mozdy AD, McCaffery JM, Shaw JM. Dnm1p GTPase-mediated mitochondrial fission is a multi-step process requiring the novel integral membrane component Fis1p. J Cell Biol. 2000 Oct 16;151(2):367-80. doi: 10.1083/jcb.151.2.367, PMID 11038183.

Qiu JZ, Yoon JH, Shen BH. Search for apoptotic nucleases in yeast: role of Tat-D nuclease in apoptotic DNA degradation. J Biol Chem. 2005 Apr 15;280(15):15370-9. doi: 10.1074/jbc.M413547200, PMID 15657035.

Ahn SH, Cheung WL, Hsu JY, Diaz RL, Smith MM, Allis CD. Sterile 20 kinase phosphorylates histone H2B at serine 10 during hydrogen peroxide-induced apoptosis in S. cerevisiae. Cell. 2005 Jan 14;120(1):25-36. doi: 10.1016/j.cell.2004.11.016, PMID 15652479.

Hochstrasser M. Ubiquitin-dependent protein degradation. Annu Rev Genet. 1996 Dec;30(1):405-39. doi: 10.1146/annurev.genet.30.1.405, PMID 8982460.

Hill SM, Hao XX, Liu BD, Nyström T. Life-span extension by a metacaspase in the yeast saccharomyces cerevisiae. Science. 2014 Jun 20;344(6190):1389-92. doi: 10.1126/science. 1252634, PMID 24855027.

Pereira C, Chaves S, Alves S, Salin B, Camougrand N, Manon S. Mitochondrial degradation in acetic acid-induced yeast apoptosis: the role of Pep4 and the ADP/ATP carrier. Mol Microbiol. 2010 Jun 11;76(6):1398-410. doi: 10.1111/j.1365-2958.2010.07122.x, PMID 20345665.

Mason DA, Shulga N, Undavai S, Ferrando-May E, Rexach MF, Goldfarb DS. Increased nuclear envelope permeability and Pep4p-dependent degradation of nucleoporins during hydrogen peroxide-induced cell death. FEMS Yeast Res. 2005 Dec 1;5(12):1237-51. doi: 10.1016/j.femsyr.2005.07.008, PMID 16183335.

Hahn JS, Thiele DJ. Regulation of the saccharomyces cerevisiae Slt2 kinase pathway by the stress-inducible Sdp1 dual-specificity phosphatase. J Biol Chem. 2002 Jun 14;277(24):21278-84. doi: 10.1074/jbc.M202557200, PMID 11923319.

Mao K, Wang K, Zhao MT, Xu T, Klionsky DJ. Two MAPK-signaling pathways are required for mitophagy in Saccharomyces cerevisiae. J Cell Biol. 2011 May 16;193(4):755-67. doi: 10.1083/jcb.201102092, PMID 21576396.

Gamon LF, Dieterich S, Ignasiak MT, Schrameyer V, Davies MJ. Iodide modulates protein damage induced by the inflammation-associated heme enzyme myeloperoxidase. Redox Biol. 2020 Jan 1;28:101331. doi: 10.1016/j.redox.2019.101331, PMID 31568923.

Ohsumi Y. Molecular dissection of autophagy: two ubiquitin-like systems. Nat Rev Mol Cell Biol. 2001 Mar 1;2(3):211-6. doi: 10.1038/35056522, PMID 11265251.

Nakatogawa H, Ichimura Y, Ohsumi Y. Atg8, a ubiquitin-like protein required for autophagosome formation, mediates membrane tethering and hemifusion. Cell. 2007 Jul 13;130(1):165-78. doi: 10.1016/j.cell.2007.05.021, PMID 17632063.

Forni C, Facchiano F, Bartoli M, Pieretti S, Facchiano A, D’Arcangelo D. Beneficial role of phytochemicals on oxidative stress and age-related diseases. BiomMed Res Int. 2019 Apr 7;2019:8748253. doi: 10.1155/2019/8748253, PMID 31080832.

Yang H, Xing R, Liu S, Yu H, Li P. Role of fucoxanthin towards cadmium-induced renal impairment with the antioxidant and anti-lipid peroxide activities. Bioengineered. 2021 Jan 1;12(1):7235-47. doi: 10.1080/21655979.2021.1973875, PMID 34569908.

Papucci L, Schiavone N, Witort E, Donnini M, Lapucci A, Tempestini A, Formigli L, Zecchi-Orlandini S, Orlandini G, Carella G, Brancato R, Capaccioli S. Coenzyme Q10 prevents apoptosis by inhibiting mitochondrial depolarization independently of its free radical scavenging property. J Biol Chem. 2003 Jul 25;278(30):28220-8. doi: 10.1074/jbc.M302297200, PMID 12736273.

Roy P, Kumar SS, Manna K, Das A. Resveratrol protects whole-body heat stress-induced testicular damage in rat model. Asian J Pharm Clin Res. 2022 March 1;15(5):27-33. doi: 10.22159/ajpcr.2022.v15i5.43968.