Microarray analysis reveals the inhibition of nuclear factor-kappa B signaling by aristolochic acid in normal human kidney (HK-2) cells
- PMID: 20139906
- PMCID: PMC4002842
- DOI: 10.1038/aps.2009.197
Microarray analysis reveals the inhibition of nuclear factor-kappa B signaling by aristolochic acid in normal human kidney (HK-2) cells
Abstract
Aim: To study the molecular mechanism underlying the effect of aristolochic acid (AA), a major active component of plants from the Aristolochiaceae family using microarray analysis.
Methods: Human kidney (HK-2) cells were treated with AA (0, 10, 30, and 90 micromol/L) for 24 h, and the cell viability was measured by a 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay. Complementary DNA microarrays were used to investigate the gene expression pattern of HK-2 cells exposed to AA in triplicate. A quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assay was used to verify the microarray data for selected nuclear factor kappa B (NF-kappaB)-regulated genes. Furthermore, the subcellular localization of NF-kappaB p65 was visualized by immunofluorescence confocal microscopy in HK-2 cells. The NF-kappaB activity was examined by a luciferase reporter assay in HK-2/NF-kappaB transgenic cells.
Results: AA exhibited a dose-dependent cytotoxic effect in HK-2 cells and induced alterations in the gene expression profiles related to the DNA damage response, DNA repair, macromolecule metabolic process, carbohydrate metabolic process, DNA metabolic process, apoptosis, cell cycle, and transcription. In addition, 9 biological pathways associated with immunomodulatory functions were down-regulated in AA-treated HK-2 cells. A network analysis revealed that NF-kappaB played a central role in the network topology. Among NF-kappaB-regulated genes, 8 differentially expressed genes were verified by qRT-PCR. The inhibition of NF-kappaB activity by AA was further confirmed by immunofluorescence confocal microscopy and by NF-kappaB luciferase reporter assay.
Conclusion: Our data revealed that AA could suppress NF-kappaB activity in normal human cells, perhaps partially accounting for the reported anti-inflammatory effects of some plants from the genus Aristolochia.
Figures




Similar articles
-
Aristolochic acid suppresses DNA repair and triggers oxidative DNA damage in human kidney proximal tubular cells.Oncol Rep. 2010 Jul;24(1):141-53. doi: 10.3892/or_00000839. Oncol Rep. 2010. PMID: 20514455
-
The Effect of Overexpression of the Enhancer of Zeste Homolog 1 (EZH1) Gene on Aristolochic Acid-Induced Injury in HK-2 Human Kidney Proximal Tubule Cells In Vitro.Med Sci Monit. 2019 Jan 28;25:801-810. doi: 10.12659/MSM.911611. Med Sci Monit. 2019. PMID: 30688289 Free PMC article.
-
Gene expression changes induced by the human carcinogen aristolochic acid I in renal and hepatic tissue of mice.Int J Cancer. 2011 Jan 1;128(1):21-32. doi: 10.1002/ijc.25324. Int J Cancer. 2011. PMID: 20232387
-
Challenges with Methods for Detecting and Studying the Transcription Factor Nuclear Factor Kappa B (NF-κB) in the Central Nervous System.Cells. 2021 May 28;10(6):1335. doi: 10.3390/cells10061335. Cells. 2021. PMID: 34071243 Free PMC article. Review.
-
NF-κB dynamics in the language of immune cells.Trends Immunol. 2023 Jan;44(1):32-43. doi: 10.1016/j.it.2022.11.005. Epub 2022 Dec 3. Trends Immunol. 2023. PMID: 36473794 Free PMC article. Review.
Cited by
-
Elucidating mechanistic insights into drug action for atopic dermatitis: a systems biology approach.BMC Dermatol. 2018 Feb 7;18(1):3. doi: 10.1186/s12895-018-0070-4. BMC Dermatol. 2018. PMID: 29415693 Free PMC article.
-
c-Jun Amino Terminal Kinase Signaling Promotes Aristolochic Acid-Induced Acute Kidney Injury.Front Physiol. 2021 Feb 12;12:599114. doi: 10.3389/fphys.2021.599114. eCollection 2021. Front Physiol. 2021. PMID: 33643061 Free PMC article.
-
Aristolochic acid I and ochratoxin A differentially regulate VEGF expression in porcine kidney epithelial cells--the involvement of SP-1 and HIFs transcription factors.Toxicol Lett. 2011 Jul 28;204(2-3):118-26. doi: 10.1016/j.toxlet.2011.04.022. Epub 2011 Apr 29. Toxicol Lett. 2011. PMID: 21554934 Free PMC article.
-
Evaluation of Antimycobacterial Activity of Higenamine Using Galleria mellonella as an In Vivo Infection Model.Nat Prod Bioprospect. 2018 Feb;8(1):63-69. doi: 10.1007/s13659-018-0152-3. Epub 2018 Jan 22. Nat Prod Bioprospect. 2018. PMID: 29357092 Free PMC article.
-
Early life stage transient aristolochic acid exposure induces behavioral hyperactivity but not nephrotoxicity in larval zebrafish.Aquat Toxicol. 2021 Sep;238:105916. doi: 10.1016/j.aquatox.2021.105916. Epub 2021 Jul 18. Aquat Toxicol. 2021. PMID: 34303159 Free PMC article.
References
-
- Rosenmund H, Reichstein T. Zur Kenntnis der Aristolochiasäure. Pharm Acta Helv. 1943;18:243–61.
-
- Debelle FD, Vanherweghem JL, Nortier JL. Aristolochic acid nephropathy: a worldwide problem. Kidney Int. 2008;74:158–69. - PubMed
-
- Zhang G, Shimokawa S, Mochizuki M, Kumamoto T, Nakanishi W, Watanabe T, et al. Chemical constituents of Aristolochia constricta: antispasmodic effects of its constituents in guinea-pig ileum and isolation of a diterpeno-lignan hybrid. J Nat Prod. 2008;71:1167–72. - PubMed
-
- Messiano GB, Vieira L, Machado MB, Lopes LM, de Bortoli SA, Zukerman-Schpector J. Evaluation of insecticidal activity of diterpenes and lignans from Aristolochia malmeana against Anticarsia gemmatalis. J Agric Food Chem. 2008;56:2655–9. - PubMed
-
- Hinou J, Demetzos C, Harvala C, Roussakis C. Cytotoxic and antimicrobial principles from the roots of Aristolochia longa. Int J Crude Drug Res. 1990;28:149–51.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases