Skip to main content

Advertisement

Log in

Coenzyme Q10 Protects Astrocytes from Ultraviolet B-Induced Damage Through Inhibition of ERK 1/2 Pathway Overexpression

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Overexpression of extracellular signal-regulated kinase ½ (ERK ½) signaling pathway leads to overproduction of reactive oxygen species (ROS) which induces oxidative stress. Coenzyme Q10 (CoQ10) scavenges ROS and protects cells against oxidative stress. The present study was designed to examine whether the protection of Coenzyme Q10 against oxidative damage in astrocytes is through regulating ERK 1/2 pathway. Ultraviolet B (UVB) irradiation was chosen as a tool to induce oxidative stress. Murine astrocytes were treated with 10 μg/ml and 25 μg/ml of CoQ10 for 24 h prior to UVB and maintained during UVB and 24 h post-UVB. Cell viability was evaluated by counting viable cells and MTT conversion assay. ROS production was measured using fluorescent probes. Levels of p-ERK 1/2, ERK 1/2, p-PKA, PKA were detected using immunocytochemistry and/or Western blotting. The results showed that UVB irradiation decreased the number of viable cells. This damaging effect was associated with accumulation of ROS and elevations of p-ERK 1/2 and p-PKA. Treatment with CoQ10 at 25 μg/ml significantly increased the number of viable cells and prevented the UVB-induced increases of ROS, p-ERK 1/2, and p-PKA. It is concluded that suppression of the PKA-ERK 1/2 signaling pathway may be one of the important mechanisms by which CoQ10 protects astrocytes from UVB-induced oxidative damage.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Molofsky AV, Krencik R, Ullian EM, Tsai HH, Deneen B, Richardson WD, Barres BA, Rowitch DH (2012) Astrocytes and disease: a neurodevelopmental perspective. Genes Dev 26:891–907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Poskanzer KE, Molofsky AV (2018) Dynamism of an astrocyte in vivo: perspectives on identity and function. Annu Rev Physiol 80:143–157

    Article  CAS  PubMed  Google Scholar 

  3. Thei L, Rocha-Ferreira E, Peebles D, Raivich G, Hristova M (2018) Extracellular signal-regulated kinase 2 has duality in function between neuronal and astrocyte expression following neonatal hypoxic-ischaemic cerebral injury. J Physiol 596:6043–6062

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Xi Y, Wang M, Zhang W, Bai M, Du Y, Zhang Z, Li Z, Miao J (2014) Neuronal damage, central cholinergic dysfunction and oxidative damage correlate with cognitive deficits in rats with chronic cerebral hypoperfusion. Neurobiol Learn Mem 109:7–19

    Article  CAS  PubMed  Google Scholar 

  5. Barteczek P, Li L, Ernst AS, Bohler LI, Marti HH, Kunze R (2017) Neuronal HIF-1alpha and HIF-2alpha deficiency improves neuronal survival and sensorimotor function in the early acute phase after ischemic stroke. J Cereb Blood Flow Metab 37:291–306

    Article  CAS  PubMed  Google Scholar 

  6. Chen X, Zhang X, Liao W, Wan Q (2017) Effect of physical and social components of enriched environment on astrocytes proliferation in rats after cerebral ischemia/reperfusion injury. Neurochem Res 42:1308–1316

    Article  CAS  PubMed  Google Scholar 

  7. Bylicky MA, Mueller GP, Day RM (2018) Mechanisms of endogenous neuroprotective effects of astrocytes in brain injury. Oxid Med Cell Longev 2018:6501031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Belanger M, Allaman I, Magistretti PJ (2011) Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab 14:724–738

    Article  CAS  PubMed  Google Scholar 

  9. Lapp DW, Zhang SS, Barnstable CJ (2014) Stat3 mediates LIF-induced protection of astrocytes against toxic ROS by upregulating the UPC2 mRNA pool. Glia 62:159–170

    Article  PubMed  Google Scholar 

  10. Zundorf G, Reiser G (2011) The phosphorylation status of extracellular-regulated kinase 1/2 in astrocytes and neurons from rat hippocampus determines the thrombin-induced calcium release and ROS generation. J Neurochem 119:1194–1204

    Article  CAS  PubMed  Google Scholar 

  11. Ito JI, Nagayasu Y, Ogawa T, Okihara H, Michikawa M (2015) Biochemical properties in membrane of rat astrocytes under oxidative stress. Brain Res 1615:1–11

    Article  CAS  PubMed  Google Scholar 

  12. Ibarretxe G, Sanchez-Gomez MV, Campos-Esparza MR, Alberdi E, Matute C (2006) Differential oxidative stress in oligodendrocytes and neurons after excitotoxic insults and protection by natural polyphenols. Glia 53:201–211

    Article  PubMed  Google Scholar 

  13. Zhang M, Gong JX, Wang JL, Jiang MY, Li L, Hu YY, Qi J, Zhang LY, Zhao H, Cui X, Xian XH, Li WB (2017) p38 MAPK participates in the mediation of GLT-1 up-regulation during the induction of brain ischemic tolerance by cerebral ischemic preconditioning. Mol Neurobiol 54:58–71

    Article  CAS  PubMed  Google Scholar 

  14. Armstead WM, Riley J, Vavilala MS (2016) Norepinephrine protects cerebral autoregulation and reduces hippocampal necrosis after traumatic brain injury via blockade of ERK MAPK and IL-6 in juvenile pigs. J Neurotrauma 33:1761–1767

    Article  PubMed  PubMed Central  Google Scholar 

  15. Zhu QL, Luo Y, Xue QS, Zhang FJ, Yu BW (2018) Different doses of sevoflurane facilitate and impair learning and memory function through activation of the ERK pathway and synthesis of ARC protein in the rat hippocampus. Brain Res 1678:174–179

    Article  CAS  PubMed  Google Scholar 

  16. Jing L, Yan R, Cao XM, He QP, Zhang JZ, Li PA (2014) PERK signaling pathway involved in lactic acid induced astrocyte damage. Int J Sci 3:29–34

    Google Scholar 

  17. Zhang JZ, Jing L, Ma Y, Guo FY, Chang Y, Li PA (2010) Monosialotetrahexosy-1 ganglioside attenuates diabetes-enhanced brain damage after transient forebrain ischemia and suppresses phosphorylation of ERK1/2 in the rat brain. Brain Res 1344:200–208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Baillie G, MacKenzie SJ, Houslay MD (2001) Phorbol 12-myristate 13-acetate triggers the protein kinase A-mediated phosphorylation and activation of the PDE4D5 cAMP phosphodiesterase in human aortic smooth muscle cells through a route involving extracellular signal regulated kinase (ERK). Mol Pharmacol 60:1100–1111

    Article  CAS  PubMed  Google Scholar 

  19. Muthukumaran K, Kanwar A, Vegh C, Marginean A, Elliott A, Guilbeault N, Badour A, Sikorska M, Cohen J, Pandey S (2018) Ubisol-Q10 (a nanomicellar water-soluble formulation of CoQ10) treatment inhibits Alzheimer-type behavioral and pathological symptoms in a double transgenic mouse (TgAPEswe, PSEN1dE9) model of Alzheimer's disease. J Alzheimers Dis 61:221–236

    Article  CAS  PubMed  Google Scholar 

  20. Sikorska M, Lanthier P, Miller H, Beyers M, Sodja C, Zurakowski B, Gangaraju S, Pandey S, Sandhu JK (2014) Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease. Neurobiol Aging 35:2329–2346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Huo J, Xu Z, Hosoe K, Kubo H, Miyahara H, Dai J, Mori M, Sawashita J, Higuchi K (2018) Coenzyme Q10 prevents senescence and dysfunction caused by oxidative stress in vascular endothelial cells. Oxid Med Cell Longev 2018:3181759

    Article  PubMed  PubMed Central  Google Scholar 

  22. Noh YH, Kim KY, Shim MS, Choi SH, Choi S, Ellisman MH, Weinreb RN, Perkins GA, Ju WK (2013) Inhibition of oxidative stress by coenzyme Q10 increases mitochondrial mass and improves bioenergetic function in optic nerve head astrocytes. Cell Death Dis 4:e820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Jing L, Kumari S, Mendelev N, Li PA (2011) Coenzyme q10 ameliorates ultraviolet B irradiation induced cell death through inhibition of mitochondrial intrinsic cell death pathway. Int J Mol Sci 12:8302–8315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Choi JS, Park SY, Yi EY, Kim YJ, Jeong JW (2011) Coenzyme Q10 decreases basic fibroblast growth factor (bFGF)-induced angiogenesis by blocking ERK activation. Oncol Res 19:455–461

    Article  CAS  PubMed  Google Scholar 

  25. Li X, Guo Y, Huang S, He M, Liu Q, Chen W, Liu M, Xu D, He P (2017) Coenzyme Q10 prevents the interleukin-1 beta induced inflammatory response via inhibition of MAPK signaling pathways in rat articular chondrocytes. Drug Dev Res 78:403–410

    Article  CAS  PubMed  Google Scholar 

  26. Jing L, He MT, Chang Y, Mehta SL, He QP, Zhang JZ, Li PA (2015) Coenzyme Q10 protects astrocytes from ROS-induced damage through inhibition of mitochondria-mediated cell death pathway. Int J Biol Sci 11:59–66

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Oliveira MM, Ratti BA (2019) Dihydrocaffeic acid prevents UVB-induced oxidative stress leading to the inhibition of apoptosis and MMP-1 expression via p38 signaling pathway. Oxid Med Cell Longev 2019:2419096

    Article  PubMed  PubMed Central  Google Scholar 

  28. Wong HS, Dighe PA, Mezera V, Monternier PA, Brand MD (2017) Production of superoxide and hydrogen peroxide from specific mitochondrial sites under different bioenergetic conditions. J Biol Chem 292:16804–16809

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Trewin AJ, Bahr LL, Almast A, Berry BJ, Wei AY, Foster TH, Wojtovich AP (2019) Mitochondrial ROS generated at the complex-II matrix or intermembrane space microdomain have distinct effects on redox signaling and stress sensitivity in C. elegans. Antioxid Redox Signal, doi: https://doi.org/10.1089/ars.2018.7681

    Article  PubMed  PubMed Central  Google Scholar 

  30. Chuang JY, Kao TJ, Lin SH, Wu AC, Lee PT, Su TP, Yeh SH, Lee YC, Wu CC, Chang WC (2017) Specificity protein 1-zinc finger protein 179 pathway is involved in the attenuation of oxidative stress following brain injury. Redox Biol 11:135–143

    Article  CAS  PubMed  Google Scholar 

  31. Mailloux RJ, Harper ME (2011) Uncoupling proteins and the control of mitochondrial reactive oxygen species production. Free Radic Biol Med 51:1106–1115

    Article  CAS  PubMed  Google Scholar 

  32. Zhu Z, Li R, Stricker R, Reiser G (2015) Extracellular alpha-crystallin protects astrocytes from cell death through activation of MAPK, PI3K/Akt signaling pathway and blockade of ROS release from mitochondria. Brain Res 1620:17–28

    Article  CAS  PubMed  Google Scholar 

  33. Ben Jilani KE, Panee J, He Q, Berry MJ, Li PA (2007) Overexpression of selenoprotein H reduces Ht22 neuronal cell death after UVB irradiation by preventing superoxide formation. Int J Biol Sci 3:198–204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Montano SJ, Grunler J, Nair D, Tekle M, Fernandes AP, Hua X, Holmgren A, Brismar K, Ungerstedt JS (2015) Glutaredoxin mediated redox effects of coenzyme Q10 treatment in type 1 and type 2 diabetes patients. BBA Clin 4:14–20

    Article  PubMed  PubMed Central  Google Scholar 

  35. Emami A, Tofighi A, Asri-Rezaei S, Bazargani-Gilani B (2018) The effect of short-term coenzyme Q10 supplementation and pre-cooling strategy on cardiac damage markers in elite swimmers. Br J Nutr 119:381–390

    Article  CAS  PubMed  Google Scholar 

  36. Erb C, Konieczka K (2018) Mitochondrial dysfunctions and role of coenzyme Q10 in patients with glaucoma. Klin Monbl Augenheilkd 235:157–162

    Article  PubMed  Google Scholar 

  37. Pegoraro NS, Barbieri AV, Camponogara C, Mattiazzi J, Brum ES, Marchiori MCL, Oliveira SM, Cruz L (2017) Nanoencapsulation of coenzyme Q10 and vitamin E acetate protects against UVB radiation-induced skin injury in mice. Colloids Surf B Biointerfaces 150:32–40

    Article  CAS  PubMed  Google Scholar 

  38. Roskoski R Jr (2012) ERK1/2 MAP kinases: structure, function, and regulation. Pharmacol Res 66:105–143

    Article  CAS  PubMed  Google Scholar 

  39. Zhang GY, Lu D, Duan SF, Gao YR, Liu SY, Hong Y, Dong PZ, Chen YG, Li T, Wang DY, Cheng XS, He F, Wei JS, Li GY, Zhang QY, Wu DD (2018) Hydrogen sulfide alleviates lipopolysaccharide-induced diaphragm dysfunction in rats by reducing apoptosis and inflammation through ROS/MAPK and TLR4/NF-kappaB signaling pathways. Oxid Med Cell Longev 2018:9647809

    PubMed  PubMed Central  Google Scholar 

  40. Zhuang S, Schnellmann RG (2006) A death-promoting role for extracellular signal-regulated kinase. J Pharmacol Exp Ther 319:991–997

    Article  CAS  PubMed  Google Scholar 

  41. Cheng P, Alberts I, Li X (2013) The role of ERK1/2 in the regulation of proliferation and differentiation of astrocytes in developing brain. Int J Dev Neurosci 31:783–789

    Article  CAS  PubMed  Google Scholar 

  42. Huang L, Li B, Tang S, Guo H, Li W, Huang X, Yan W, Zou F (2015) Mitochondrial KATP channels control glioma radioresistance by regulating ROS-induced ERK activation. Mol Neurobiol 52:626–637

    Article  CAS  PubMed  Google Scholar 

  43. Dai H, Song D, Xu J, Li B, Hertz L, Peng L (2013) Ammonia-induced Na, K-ATPase/ouabain-mediated EGF receptor transactivation, MAPK/ERK and PI3K/AKT signaling and ROS formation cause astrocyte swelling. Neurochem Int 63:610–625

    Article  CAS  PubMed  Google Scholar 

  44. Zhuang S, Yan Y, Daubert RA, Han J, Schnellmann RG (2007) ERK promotes hydrogen peroxide-induced apoptosis through caspase-3 activation and inhibition of Akt in renal epithelial cells. Am J Physiol Renal Physiol 292:F440–447

    Article  CAS  PubMed  Google Scholar 

  45. Kano G, Almanan M, Bochner BS, Zimmermann N (2013) Mechanism of siglec-8-mediated cell death in IL-5-activated eosinophils: role for reactive oxygen species-enhanced MEK/ERK activation. J Allergy Clin Immunol 132:437–445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Lefkimmiatis K, Zaccolo M (2014) cAMP signaling in subcellular compartments. Pharmacol Ther 143:295–304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Waltereit R, Weller M (2003) Signaling from cAMP/PKA to MAPK and synaptic plasticity. Mol Neurobiol 27:99–106

    Article  CAS  PubMed  Google Scholar 

  48. Wu W, Yin Y, Xu K, Peng Y, Zhang J (2018) Knockdown of LGALS12 inhibits porcine adipocyte adipogenesis via PKA-Erk1/2 signaling pathway. Acta Biochim Biophys Sin (Shanghai) 50:960–967

    Article  CAS  Google Scholar 

  49. Li L, Ge C, Wang D, Yu L, Zhao J, Ma H (2018) Dehydroepiandrosterone reduces accumulation of lipid droplets in primary chicken hepatocytes by biotransformation mediated via the cAMP/PKA-ERK1/2 signaling pathway. Biochim Biophys Acta Mol Cell Biol Lipids 1863:625–638

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by the National Natural Science Foundation of China (Nos. 31780280, 81560208) and West China first-class Disciplines Basic Medical Sciences at Ningxia Medical University (No. NXYLXK2017B07).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to P. Andy Li or Jian-Zhong Zhang.

Ethics declarations

Conflict of interest

The authors have declared that no competing interest exists.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, Q., Ma, YM., Jing, L. et al. Coenzyme Q10 Protects Astrocytes from Ultraviolet B-Induced Damage Through Inhibition of ERK 1/2 Pathway Overexpression. Neurochem Res 44, 1755–1763 (2019). https://doi.org/10.1007/s11064-019-02812-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-019-02812-6

Keywords

Navigation