CXCL12 Protects Pancreatic β-cells from Oxidative Stress by a Nrf2-induced Increase in Catalase Expression and Activity

Overview

Journal Proc Jpn Acad Ser B Phys Biol Sci

Specialties Biology
Science

Date 2016 Nov 15

PMID 27840391

Citations 14

Authors

Svetlana Dinic

Nevena Grdovic

Aleksandra Uskokovic

Milos Dordevic

Mirjana Mihailovic

Jelena Arambasic Jovanovic

Goran Poznanovic

Melita Vidakovic

Affiliations

Soon will be listed here.

Abstract

Due to intrinsically low levels of antioxidant enzyme expression and activity, insulin producing pancreatic β-cells are particularly susceptible to free radical attack. In diabetes mellitus, which is accompanied by high levels of oxidative stress, this feature of β-cells significantly contributes to their damage and dysfunction. In light of the documented pro-survival effect of chemokine C-X-C Ligand 12 (CXCL12) on pancreatic β-cells, we examined its potential role in antioxidant protection. We report that CXCL12 overexpression enhanced the resistance of rat insulinoma (Rin-5F) and primary pancreatic islet cells to hydrogen peroxide (HO). CXCL12 lowered the levels of DNA damage and lipid peroxidation and preserved insulin expression. This effect was mediated through an increase in catalase (CAT) activity. By activating downstream p38, Akt and ERK kinases, CXCL12 facilitated Nrf2 nuclear translocation and enhanced its binding to the CAT gene promoter, inducing constitutive CAT expression and activity that was essential for protecting β-cells from HO.

Citing Articles

Exploring the key role of DNA methylation as an epigenetic modulator in oxidative stress related islet cell injury in patients with type 2 diabetes mellitus: a review.

Ahmed I, Chakraborty R, Faizy A, Moin S J Diabetes Metab Disord. 2024; 23(2):1699-1718.

PMID: 39610516 PMC: 11599646. DOI: 10.1007/s40200-024-01496-2.

Targeting catalase in cancer.

Glorieux C, Buc Calderon P Redox Biol. 2024; 77:103404.

PMID: 39447253 PMC: 11539659. DOI: 10.1016/j.redox.2024.103404.

Nrf2 and Ferroptosis: Exploring Translational Avenues for Therapeutic Approaches to Neurological Diseases.

Mohan M, Mannan A, Kakkar C, Singh T Curr Drug Targets. 2024; 26(1):33-58.

PMID: 39350404 DOI: 10.2174/0113894501320839240918110656.

Functional transcriptome analysis revealed major changes in pathways affecting systems biology of Tharparkar cattle under seasonal heat stress.

Singh A, Verma A, Dutta G, Gowane G, Ludri A, Alex R 3 Biotech. 2024; 14(7):177.

PMID: 38855148 PMC: 11156831. DOI: 10.1007/s13205-024-04018-2.

SAP deletion promotes malignant insulinoma progression by inducing CXCL12 secretion from CAFs via the CXCR4/p38/ERK signalling pathway.

Jiang G, Xu S, Mai X, Tu J, Wang L, Wang L J Cell Mol Med. 2024; 28(10):e18397.

PMID: 38766687 PMC: 11103456. DOI: 10.1111/jcmm.18397.

References

Xu B, Moritz J, Epstein P . Overexpression of catalase provides partial protection to transgenic mouse beta cells. Free Radic Biol Med. 1999; 27(7-8):830-7. DOI: 10.1016/s0891-5849(99)00130-6. View

Pi J, Zhang Q, Fu J, Woods C, Hou Y, Corkey B . ROS signaling, oxidative stress and Nrf2 in pancreatic beta-cell function. Toxicol Appl Pharmacol. 2009; 244(1):77-83. PMC: 2837798. DOI: 10.1016/j.taap.2009.05.025. View

Markovic J, Grdovic N, Dinic S, Karan-Djurasevic T, Uskokovic A, Arambasic J . PARP-1 and YY1 are important novel regulators of CXCL12 gene transcription in rat pancreatic beta cells. PLoS One. 2013; 8(3):e59679. PMC: 3608566. DOI: 10.1371/journal.pone.0059679. View

Hoffmann A, Natoli G, Ghosh G . Transcriptional regulation via the NF-kappaB signaling module. Oncogene. 2006; 25(51):6706-16. DOI: 10.1038/sj.onc.1209933. View

Nti B, Markman J, Bertera S, Styche A, Lakomy R, Subbotin V . Treg cells in pancreatic lymph nodes: the possible role in diabetogenesis and β cell regeneration in a T1D model. Cell Mol Immunol. 2012; 9(6):455-63. PMC: 4002217. DOI: 10.1038/cmi.2012.36. View

Robertson R, Zhou H, Zhang T, Harmon J . Chronic oxidative stress as a mechanism for glucose toxicity of the beta cell in type 2 diabetes. Cell Biochem Biophys. 2007; 48(2-3):139-46. DOI: 10.1007/s12013-007-0026-5. View

Song M, Kim E, Moon W, Park J, Kim H, So H . Sulforaphane protects against cytokine- and streptozotocin-induced beta-cell damage by suppressing the NF-kappaB pathway. Toxicol Appl Pharmacol. 2008; 235(1):57-67. DOI: 10.1016/j.taap.2008.11.007. View

Itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y . An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun. 1997; 236(2):313-22. DOI: 10.1006/bbrc.1997.6943. View

Zipper L, Mulcahy R . Inhibition of ERK and p38 MAP kinases inhibits binding of Nrf2 and induction of GCS genes. Biochem Biophys Res Commun. 2000; 278(2):484-92. DOI: 10.1006/bbrc.2000.3830. View

10.

Vaziri N . Protective effect of Nrf2 and catalase in maternal diabetes-induced perinatal hypertension and kidney disease. Diabetes. 2012; 61(10):2400-2. PMC: 3447916. DOI: 10.2337/db12-0764. View

11.

Liu Z, Stanojevic V, Avadhani S, Yano T, Habener J . Stromal cell-derived factor-1 (SDF-1)/chemokine (C-X-C motif) receptor 4 (CXCR4) axis activation induces intra-islet glucagon-like peptide-1 (GLP-1) production and enhances beta cell survival. Diabetologia. 2011; 54(8):2067-76. PMC: 4111228. DOI: 10.1007/s00125-011-2181-x. View

12.

Poynter M, Baeuerle P . Recent advances towards understanding redox mechanisms in the activation of nuclear factor kappaB. Free Radic Biol Med. 2000; 28(9):1317-27. DOI: 10.1016/s0891-5849(00)00218-5. View

13.

St Clair D, Porntadavity S, Xu Y, Kiningham K . Transcription regulation of human manganese superoxide dismutase gene. Methods Enzymol. 2002; 349:306-12. DOI: 10.1016/s0076-6879(02)49345-7. View

14.

Yagishita Y, Fukutomi T, Sugawara A, Kawamura H, Takahashi T, Pi J . Nrf2 protects pancreatic β-cells from oxidative and nitrosative stress in diabetic model mice. Diabetes. 2013; 63(2):605-18. DOI: 10.2337/db13-0909. View

15.

Nadal A, Rovira J, Laribi O, Leon-Quinto T, Andreu E, Ripoll C . Rapid insulinotropic effect of 17beta-estradiol via a plasma membrane receptor. FASEB J. 1998; 12(13):1341-8. DOI: 10.1096/fasebj.12.13.1341. View

16.

Rojo A, Sagarra M, Cuadrado A . GSK-3beta down-regulates the transcription factor Nrf2 after oxidant damage: relevance to exposure of neuronal cells to oxidative stress. J Neurochem. 2007; 105(1):192-202. DOI: 10.1111/j.1471-4159.2007.05124.x. View

17.

Xia Z, Dickens M, Raingeaud J, Davis R, Greenberg M . Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science. 1995; 270(5240):1326-31. DOI: 10.1126/science.270.5240.1326. View

18.

Hui L, Bakiri L, Stepniak E, Wagner E . p38alpha: a suppressor of cell proliferation and tumorigenesis. Cell Cycle. 2007; 6(20):2429-33. DOI: 10.4161/cc.6.20.4774. View

19.

Lenzen S . Oxidative stress: the vulnerable beta-cell. Biochem Soc Trans. 2008; 36(Pt 3):343-7. DOI: 10.1042/BST0360343. View

20.

Taniguchi M, Hashimoto M, Hori N, Sato K . CCAAT/enhancer binding protein-beta (C/EBP-beta), a pivotal regulator of the TATA-less promoter in the rat catalase gene. FEBS Lett. 2005; 579(25):5785-90. DOI: 10.1016/j.febslet.2005.09.068. View