Lupeol is known to be plentiful in fruits or plant barks and has an antimicrobial effect, however, its mode of action(s) has yet to be determined. To elucidate lupeol generates nitric oxide (NO), which is recognized for possessing an antimicrobial activity, intracellular NO was measured in Escherichia coli using DAF-FM. Using the properties of NO passing through plasma membrane easily, increased malondialdehyde levels have shown that lupeol causes lipid peroxidation, and the resulting membrane depolarization was confirmed by DiBAC4(3). These data indicated that lupeol-induced NO is related to the destruction of bacterial membrane. Further study was performed to examine whether NO, known as a cell proliferation inhibitor, affects bacterial cell division. As a result, DAPI staining verified that lupeol promotes cell division arrest, and followed by early apoptosis is observed in Annexin V/PI double staining. Even though these apoptotic hallmarks appeared, the endonuclease failed to perform properly with supporting data of decreased intracellular Mg2+ and Ca2+ levels without DNA fragmentation, which is confirmed using a TUNEL assay. These findings indicated that lupeol-induced NO occurs DNA fragmentation-independent bacterial apoptosis-like death (ALD). Additionally, lupeol triggers DNA filamentation and morphological changes in response to DNA repair system called SOS system. In accordance with the fact that ALD deems to SOS response, and that the RecA is considered as a caspase-like protein, increase in caspase-like protein activation occurred in E. coli wild-type, and no ΔRecA mutant. In conclusion, these results demonstrated that the antibacterial mode of action(s) of lupeol is an ALD while generating NO.
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In the brain, cocaine exposure results in mitochondrial DNA damage, depletion of ATP and increased oxidative stress, coupled with increased mitochondrial fission. Therapies preventing such bioenergetic impairment may hold promise in mitigating cocaine pathology and addiction. You can read more about this in the review by Thornton and colleagues (pp. 749–764) in this issue. Image provided by Claire Thornton.
Research Article|
February 24 2021
Lupeol-induced nitric oxide elicits apoptosis-like death within Escherichia coli in a DNA fragmentation-independent manner
Heesu Kim;
Heesu Kim
Conceptualization, Resources, Data curation, Formal analysis, Validation, Investigation, Methodology, Writing - original draft, Project administration, Writing - review & editing
School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Korea
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Dong Gun Lee
Conceptualization, Formal analysis, Supervision, Investigation, Writing - original draft, Project administration, Writing - review & editing
School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Korea
Correspondence: Dong Gun Lee (dglee222@knu.ac.kr)
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Publisher: Portland Press Ltd
Received:
November 21 2020
Revision Received:
January 25 2021
Accepted:
February 01 2021
Accepted Manuscript online:
February 01 2021
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2021
Biochem J (2021) 478 (4): 855–869.
Article history
Received:
November 21 2020
Revision Received:
January 25 2021
Accepted:
February 01 2021
Accepted Manuscript online:
February 01 2021
Citation
Heesu Kim, Dong Gun Lee; Lupeol-induced nitric oxide elicits apoptosis-like death within Escherichia coli in a DNA fragmentation-independent manner. Biochem J 26 February 2021; 478 (4): 855–869. doi: https://doi.org/10.1042/BCJ20200925
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