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Article

Acetyl‑l‑carnitine prevents homocysteine‑induced suppression of Nrf2/Keap1 mediated antioxidation in human lens epithelial cells

  • Authors:
    • Shui‑Ping Yang
    • Xiu‑Zhen Yang
    • Guo‑Ping Cao
  • View Affiliations / Copyright

    Affiliations: Department of Ophthalmology, Taizhou People's Hospital, Taizhou, Jiangsu 225499, P.R. China, Department of Hepatic Disease, Taizhou People's Hospital, Taizhou, Jiangsu 225499, P.R. China
  • Pages: 1145-1150
    |
    Published online on: March 13, 2015
       https://doi.org/10.3892/mmr.2015.3490
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Abstract

Previous studies have revealed that high levels of serum homocysteine (Hcy) are closely associated with the development of juvenile and age‑related cataracts. An increased concentration of Hcy is likely to induce gene specific demethylation in DNA promoter regions. The aim of the present study was to prevent this demethylation by administering acetyl‑l‑carnitine (ALCAR) to human lens epithelial cells (HLECs). Different concentrations of Hcy were used to treat HLECs for 3, 6, 12 and 24 h and the findings were used to determine the optimum dose to induce endoplasmic reticulum (ER) stress. Similarly, the concentration of ALCAR was standardized. The production of reactive oxygen species (ROS) and the percentage of cells undergoing cell death were measured. The levels of antioxidants, ER stress‑associated proteins, mRNA levels of nuclear factor erythroid‑2‑related factor 2 (Nrf2), Kelch‑like ECH‑associated protein 1 (Keap1) and promoter DNA methylation of the Keap1 gene were also assessed. Hcy was observed to induce ER stress, produce ROS and lead to cell death. However, administration of ALCAR prevented these effects to a significant degree. Additionally, western blot analysis revealed that ALCAR increased the levels of antioxidant proteins, including catalase, superoxide dismutase, glutathione peroxidase, Nrf2, Keap1 and glutathione. Similarly, the reverse transcription‑quantitative polymerase chain reaction experiments on Nrf2 and Keap1, as well as the bisulfite genomic DNA sequencing analysis revealed a preventive effect of ALCAR against Hcy‑induced ER stress. The ER stress‑induced activation of the unfolded protein response is responsible for demethylation of Keap1 promoter DNA to activate the expression of the Keap1 protein, which then increases the targeting of Nrf2 for proteosomal degradation. This decrease in Nrf2 activity represses the transcription of numerous antioxidant enzyme genes and alters the redox‑balance towards lens oxidation. However, treatment with ALCAR led to significant protection from these effects. The present results suggested that ALCAR either prevents or ameliorates the actions of the antioxidant system in HLECs at the level of the protein and the gene. Further advanced studies are required for the development of ALCAR as an anti‑cataract agent.
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1 

Sen SK, Pukazhvanthen P and Abraham R: Plasma homo-cysteine, folate and vitamin B(12) levels in senile cataract. Indian J Clin Biochem. 23:255–257. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Sulochana KN, Amirthalakshmi S, Vasanthi SB, et al: Homocystinuria with congenital/developmental cataract. Indian J Pediatr. 67:725–728. 2000. View Article : Google Scholar : PubMed/NCBI

3 

Cumurcu T, Sahin S and Aydin E: Serum homocysteine, vitamin B 12 and folic acid levels in different types of glaucoma. BMC Ophthalmol. 6:62006. View Article : Google Scholar : PubMed/NCBI

4 

Selhub J: Homocysteine metabolism. Annu Rev Nutr. 19:217–246. 1999. View Article : Google Scholar : PubMed/NCBI

5 

Williams KT and Schalinske KL: Homocysteine metabolism and its relation to health and disease. Biofactors. 36:19–24. 2010.PubMed/NCBI

6 

Ron D and Walter P: Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 8:519–529. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Todd DJ, Lee AH and Glimcher LH: The endoplasmic reticulum stress response in immunity and autoimmunity. Nat Rev Immunol. 8:663–674. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Elanchezhian R, Palsamy P, Madson CJ, et al: Low glucose under hypoxic conditions induces unfolded protein response and produces reactive oxygen species in lens epithelial cells. Cell Death Dis. 3:e3012012. View Article : Google Scholar : PubMed/NCBI

9 

Ikesugi K, Yamamoto R, Mulhern ML and Shinohara T: Role of the unfolded protein response (UPR) in cataract formation. Exp Eye Res. 83:508–516. 2006. View Article : Google Scholar : PubMed/NCBI

10 

Elanchezhian R, Palsamy P, Madson CJ, Lynch DW and Shinohara T: Age-related cataracts: homocysteine coupled endoplasmic reticulum stress and suppression of Nrf2-dependent antioxidant protection. Chem Biol Interact. 200:1–10. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Huang HC, Nguyen T and Pickett CB: Phosphorylation of Nrf2 at Ser-40 by protein kinase C regulates antioxidant response element-mediated transcription. J Biol Chem. 277:42769–42774. 2002. View Article : Google Scholar : PubMed/NCBI

12 

Enomoto A, Itoh K, Nagayoshi E, et al: High sensitivity of Nrf2 knockout mice to acetaminophen hepatotoxicity associated with decreased expression of ARE-regulated drug metabolizing enzymes and antioxidant genes. Toxicol Sci. 59:169–177. 2001. View Article : Google Scholar : PubMed/NCBI

13 

Kaspar JW, Niture SK and Jaiswal AK: Nrf2:INrf2 (Keap1) signaling in oxidative stress. Free Radic Biol Med. 47:1304–1309. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Gao Y, Yan Y and Huang T: Human age-related cataracts: Epigenetic suppression of the nuclear factor erythroid 2-related factor 2-mediated antioxidant system. Mol Med Rep. 11:1442–1447. 2015.

15 

Peluso G, Petillo O, Barbarisi A, et al: Carnitine protects the molecular chaperone activity of lens alpha-crystallin and decreases the protein post-translational modifications induced by oxidative stress. FASEB J. 15:1604–1606. 2001.PubMed/NCBI

16 

Riccioloni R, Scalibastri M, Kelleher JK, et al: Role of acetyl-L-carnitine in rat brain lipogenesis: implications for polyunsaturated fatty acid biosynthesis. J Neurochem. 71:2510–2517. 1998. View Article : Google Scholar

17 

Zhou P, Chen Z, Zhao N, et al: Acetyl-L-carnitine attenuates homocysteine-induced Alzheimer-like histopathological and behavioral abnormalities. Rejuvenation Res. 14:669–679. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Elanchezhian R, Ramesh E, Sakthivel M, et al: Acetyl-L-carnitine prevents selenite-induced cataractogenesis in an experimental animal model. Curr Eye Res. 32:961–971. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Elanchezhian R, Sakthivel M, Geraldine P and Thomas PA: The effect of acetyl-L-carnitine on lenticular calpain activity in prevention of selenite-induced cataractogenesis. Exp Eye Res. 88:938–944. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Bradford MM: 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. 1976. View Article : Google Scholar : PubMed/NCBI

21 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar

22 

Rohde C, Zhang Y, Reinhardt R and Jeltsch A: BISMA - fast and accurate bisulfite sequencing data analysis of individual clones from unique and repetitive sequences. BMC Bioinformatics. 11:2302010. View Article : Google Scholar :

23 

Elanchezhian R, Sakthivel M, Geraldine P and Thomas PA: Regulatory effect of acetyl-l-carnitine on expression of lenticular antioxidant and apoptotic genes in selenite-induced cataract. Chem Biol Interact. 184:346–351. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Brennan LA and Kantorow M: Mitochondrial function and redox control in the aging eye: role of MsrA and other repair systems in cataract and macular degenerations. Exp Eye Res. 88:195–203. 2009. View Article : Google Scholar :

25 

Lou MF: Redox regulation in the lens. Prog Retin Eye Res. 22:657–682. 2003. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yang SP, Yang XZ and Cao GP: Acetyl‑l‑carnitine prevents homocysteine‑induced suppression of Nrf2/Keap1 mediated antioxidation in human lens epithelial cells. Mol Med Rep 12: 1145-1150, 2015.
APA
Yang, S., Yang, X., & Cao, G. (2015). Acetyl‑l‑carnitine prevents homocysteine‑induced suppression of Nrf2/Keap1 mediated antioxidation in human lens epithelial cells. Molecular Medicine Reports, 12, 1145-1150. https://doi.org/10.3892/mmr.2015.3490
MLA
Yang, S., Yang, X., Cao, G."Acetyl‑l‑carnitine prevents homocysteine‑induced suppression of Nrf2/Keap1 mediated antioxidation in human lens epithelial cells". Molecular Medicine Reports 12.1 (2015): 1145-1150.
Chicago
Yang, S., Yang, X., Cao, G."Acetyl‑l‑carnitine prevents homocysteine‑induced suppression of Nrf2/Keap1 mediated antioxidation in human lens epithelial cells". Molecular Medicine Reports 12, no. 1 (2015): 1145-1150. https://doi.org/10.3892/mmr.2015.3490
Copy and paste a formatted citation
x
Spandidos Publications style
Yang SP, Yang XZ and Cao GP: Acetyl‑l‑carnitine prevents homocysteine‑induced suppression of Nrf2/Keap1 mediated antioxidation in human lens epithelial cells. Mol Med Rep 12: 1145-1150, 2015.
APA
Yang, S., Yang, X., & Cao, G. (2015). Acetyl‑l‑carnitine prevents homocysteine‑induced suppression of Nrf2/Keap1 mediated antioxidation in human lens epithelial cells. Molecular Medicine Reports, 12, 1145-1150. https://doi.org/10.3892/mmr.2015.3490
MLA
Yang, S., Yang, X., Cao, G."Acetyl‑l‑carnitine prevents homocysteine‑induced suppression of Nrf2/Keap1 mediated antioxidation in human lens epithelial cells". Molecular Medicine Reports 12.1 (2015): 1145-1150.
Chicago
Yang, S., Yang, X., Cao, G."Acetyl‑l‑carnitine prevents homocysteine‑induced suppression of Nrf2/Keap1 mediated antioxidation in human lens epithelial cells". Molecular Medicine Reports 12, no. 1 (2015): 1145-1150. https://doi.org/10.3892/mmr.2015.3490
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