Skip to main content

Advertisement

SpringerLink
Log in

Cholinergic Precursors Modulate the Expression of Heme Oxigenase-1, p21 During Astroglial Cell Proliferation and Differentiation in Culture

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

Abstract

Heme oxygenase-1 (HO-1) plays a crucial role in oxidative stress processes, apoptosis and cell differentiation. Further, some proteins related to cell cycle including cyclins and p21 are important markers of astrocyte cultures. Aim of investigation was to study the effects of cholinergic precursors (choline, CDP-choline, Acetylcholine and α-Glyceril-Phosphorylcholine) on HO-1 and p21 expression during astroglial cell proliferation and differentiation in primary cultures at 14 and 35 days in vitro (DIV) treated for 24 h with choline metabolites. Our results showed a slight reduction of HO-1 expression (data not statistical significant) in astroglial cell cultures treated with CDP-choline at 14 DIV and 35 DIV. On the contrary, ACh and choline induced a significant increase of HO-1 expression in 14 DIV astrocyte cultures. Surprisingly, choline and ACh dramatically reduced HO-1 expression at 35 DIV. A slight decrease not statistical significant was detectable for α-GPC at 14 DIV and particularly significant at 35 DIV. Data concerning p21 expression, a well known protein inhibiting cell cycle, evidenced a significant increase at 14 and 35 DIV after α-GPC treatment. CDP-choline treatment caused a high increase of p21 expression in 14 DIV astrocyte cultures, but no modification at 35 DIV. Instead, ACh treatment induced a marked increment of p21 expression at 35 DIV. Our data suggest that cholinergic precursors modulate HO-1 and p21 expression during astroglial cell proliferation and differentiation in culture and could be considered a tool to study the induced effects of ischemia and hypoxia diseases in some in vitro models to prevent and reduce its effects after treatment with cholinergic drugs.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Takasaki I, Satoko T, Mamoru F et al (2007) Identification of genetic networks involved in the cell growth arrest and differentiation of a rat astrocyte cell line. J Cell Biochem 102:1472–1485. doi:10.1002/jcb.21369

    Article  PubMed  CAS  Google Scholar 

  2. Carnevale D, De Simone R, Minghetti L (2007) Microglia-neuron interaction in inflammatory and degenerative diseases: role of cholinergic and noradrenergic systems. CNS Neurol Disord Drug Targets 6:388–397 1871-5273/07. doi:10.2174/187152707783399193

  3. Bessis A, Bechade C, Bernard D, Roumier A (2007) Microglia-neuron interaction in inflammatory and degenerative diseases: role of cholinergic and noradrenergic systems. CNS Neurol Disord Drug Targets 6:388–397 1871-5273/07. doi:10.2174/187152707783399193

  4. Bramanti V, Bronzi D, Tomassoni D et al (2008) Growth factors and steroid mediated regulation of cytoskeletal protein expression in serum-deprived primary astrocyte cultures. Neurochem Res 33(12):2601–2608. doi:10.1007/s11064-008-9829-z

    Article  PubMed  CAS  Google Scholar 

  5. Sharma G, Vijayaraghavan S (2001) Nicotinic cholinergic signaling in hippocampal astrocytes involves calcium-induced calcium release from intracellular stores. Proc Natl Acad Sci USA 98:4148–4153. doi:10.1073/pnas.071540198

    Article  PubMed  CAS  Google Scholar 

  6. Seigneur J, Kroeger D, Nita DA, Amzica F (2006) Cholinergic action on cortical glial cells in vivo. Cereb Cortex 16:655–668. doi:10.1093/cercor/bhj011

    Article  PubMed  Google Scholar 

  7. Parnetti L, Mignini F, Tomassoni D, Traini E, Amenta F (2007) Cholinergic precursors in the treatment of cognitive impairment of vascular origin: ineffective approaches or need for re-evaluation? J Neurol Sci 257:264–269. doi:10.1016/j.jns.2007.01.043

    Article  PubMed  CAS  Google Scholar 

  8. Amenta F, Tayebati SK (2008) Pathways of acetylcholine synthesis, transport and release as targets for treatment of adult-onset cognitive dysfunction. Curr Med Chem 15:488–498. doi:10.2174/092986708783503203

    Article  PubMed  CAS  Google Scholar 

  9. Li Volti G, Ientile RG, Abraham N et al (2004) Immunocytochemical localization and expression of heme oxygenase-1 in primary astroglial cell cultures during differentiation: effect of glutamate. J Biochem Biophys Res Commun 315(2004):517–524. doi:10.1016/j.bbrc.2004.01.090

    Article  CAS  Google Scholar 

  10. Eisenstein RS, Garcia-Mayol D, Pettingell W, Munro HN (1991) Regulation of ferritin and heme oxygenase synthesis in rat fibroblasts by different forms of iron. Proc Natl Acad Sci USA 88:688–692

    Article  PubMed  CAS  Google Scholar 

  11. Shibahara S, Yoshizawa M, Suzuki H et al (1993) Functional analysis of cDNAs for two types of human heme oxygenase and evidence for their separate regulation. J Biochem (Tokyo) 113:214–218

    CAS  Google Scholar 

  12. Abraham NG, Lin JH, Schwartzman ML et al (1988) The physiological significance of heme oxygenase. Int J Biochem 20:543–558. doi:10.1016/0020-711X(88)90093-6

    Article  PubMed  CAS  Google Scholar 

  13. McCoubrey WK Jr, Ewing JF, Maines MD (1992) Human heme oxygenase-2: characterization and expression of a full-length cDNA and evidence suggesting that the two HO-2 transcripts may differ by choice of polyadenylation signal. Arch Biochem Biophys 295:13–20. doi:10.1016/0003-9861(92)90481-B

    Article  PubMed  CAS  Google Scholar 

  14. Li Volti G, Seta F, Schwartzman ML et al (2003) Heme oxygenase attenuates angiotensin II-mediated increase in cyclooxygenase-2 activity in human femoral endothelial cells. Hypertension 41:715–719. doi:10.1161/01.HYP.0000049163.23426.66

    Article  PubMed  CAS  Google Scholar 

  15. Kushida T, Li Volti G, Goodman AI et al (2002) TNF alpha-mediated cell death is attenuated by retrovirus delivery of human heme oxygenase-1 gene into human microvessel endothelial cells. Transplant Proc 34:2973–2978. doi:10.1016/S0041-1345(02)03506-6

    Article  PubMed  CAS  Google Scholar 

  16. Kushida T, Li Volti G, Quan S et al (2002) Role of human heme oxygenase-1 in attenuating TNF-alpha mediated inflammation injury in endothelial cells. J Cell Biochem 87:377–385. doi:10.1002/jcb.10316

    Article  PubMed  CAS  Google Scholar 

  17. Lavrovsky Y, Schwartzman ML, Abraham NG (1993) Novel regulatory sites of the human heme oxygenase-1 promoter region. Biochem Biophys Res Commun 196:336–341. doi:10.1006/bbrc.1993.2253

    Article  PubMed  CAS  Google Scholar 

  18. Cragnolini A.B, Volosin M, Huang Y et al (2011) Nerve Growth Factor Induces Cell Cycle Arrest of Astrocytes. Dev Neurobiol doi:10.1002/dneu.20981

  19. Sherr CJ (1993) Mammalian G1 cyclins. Cell 73:1059–1065. doi:10.1016/0092-8674(93)90636-5

    Article  PubMed  CAS  Google Scholar 

  20. Obaya AJ, Sedivy JM (2002) Regulation of cyclin-Cdk activity in mammalian cells. Cell Mol Life Sci 59(2002):126–142. doi:10.1007/s00018-002-8410-1

    Article  PubMed  CAS  Google Scholar 

  21. Serrano M, Hannon GJ, Beach D (1993) A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 366(6456):704–707. doi:10.1038/366704a0

    Article  PubMed  CAS  Google Scholar 

  22. Cánepa ET, Scassa ME, Ceruti JM, Marazita MC, Carcagno AL, Sirkin PF, Ogara MF (2007) INK4 proteins, a family of mammalian CDK inhibitors with novel biological functions. IUBMB Life 59(7):419–426. doi:10.1080/15216540701488358

    Article  PubMed  Google Scholar 

  23. Sherr CJ, Roberts JM (1995) Inhibitors of mammalian G1 cyclindependent kinases. Genes Dev 9:1149–1163. doi:10.1101/gad.9.10.1149

    Article  PubMed  CAS  Google Scholar 

  24. Sherr CJ, Roberts JM (1999) CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 13(12):1501–1512. doi:10.1101/gad.13.12.1501

    Article  PubMed  CAS  Google Scholar 

  25. Moon DO, Choi YH, Kim GY (2011) Role of p21 in SP600125-induced cell cycle arrest, endoreduplication and apoptosis. Cell Mol Life Sci 68(19):3249–3260

    Google Scholar 

  26. Waga S, Hannon GJ, Beach D, Stillman B (1994) The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature 369:574–578. doi:10.1038/369574a0

    Article  PubMed  CAS  Google Scholar 

  27. Parker SB, Eichele G, Zhang P, Rawls A, Sands AT, Bradley A, Olson EN, Harper JW, Elledge SJ (1995) p53-independent expression of p21Cip1 in muscle and other terminally differentiating cells. Science 267:1024–1027. doi:10.1126/science.7863329

    Article  PubMed  CAS  Google Scholar 

  28. Gartel AL, Tyner AL (1999) Transcriptional regulation of the p21(WAF1/CIP1) gene. Exp Cell Res 246:280–289. doi:10.1006/excr.1998.4319

    Article  PubMed  CAS  Google Scholar 

  29. el-Deiry WS, Tokino T, Velculescu VE et al (1993) WAF1, a potential mediator of p53 tumor suppression. Cell 75:817–825. doi:10.1016/0092-8674(93)90500-P

    Article  PubMed  CAS  Google Scholar 

  30. Bramanti V, Tomassoni D, Bronzi D et al (2010) Alpha-lipoic acid modulates GFAP, vimentin, nestin, cyclin D1 and MAP-kinase espression in astroglial cell cultures. Neurochem Res 35(12):2070–2077. doi:10.1007/s11064-010-0256-6

    Article  PubMed  CAS  Google Scholar 

  31. Bramanti V, Campisi A, Tomassoni D et al (2008) Effect of acetylcholine precursors on proliferation and differentiation of astroglial cells in primary cultures. Neurochem Res 33(12):2601–2608. doi:10.1007/s11064-008-9829-z

    Article  PubMed  CAS  Google Scholar 

  32. Gray JW, Pallavicini MG, George YS et al (1981) Rates of incorporation of radioactive molecules during the cell cycle. J Cell Physiol 108(2):135–144. doi:10.1002/jcp1041080204

    Article  PubMed  CAS  Google Scholar 

  33. Bramanti V, Bronzi D, Tomassoni D, Li Volti G, Cannavò G, Raciti G, Napoli M, Vanella A, Campisi A, Ientile R, Avola R (2008) Effect of choline-containing phospholipids on transglutaminase activity in primary astroglial cell cultures. Clin Exp Hypertens 30(8):798–807. doi:10.1080/10641960802563576

    Article  PubMed  CAS  Google Scholar 

  34. Clarck W, Gunion-Rinker L, Lessov N et al (1998) Citicoline treatment for experimental intracerebral hemorrhage in mice. Stroke 29:2136–2140. doi:10.1161/01.STR.29.10.2136

    Article  Google Scholar 

  35. Alvarez-Sabín J, Román GC (2011) Citicoline in vascular cognitive impairment and vascular dementia after stroke. Stroke 42(1 Suppl):S40–S43. Epub 2010 Dec 16. Review. doi:10.1161/STROKEAHA.110.606509

    Google Scholar 

Download references

Acknowledgments

The authors thank very much the pharmaceutical company’s MDM S.p.A. (MB), Italy (mail: mdm@mdmspa.com), for the financial support given to Prof. Roberto Avola’s research group and particularly to Dr. Roberto Gabriele.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Chemical Sciences, Section Biochemistry and Molecular Biology, University of Catania, Viale A. Doria 6, 95125, Catania, Italy

    V. Bramanti, S. Grasso, D. Bronzi & R. Avola

  2. School of Pharmacy, Section of Human Anatomy, University of Camerino, Camerino, MC, Italy

    D. Tomassoni & F. Amenta

  3. Department of Biochemical, Physiological and Nutritional Sciences, University of Messina, Messina, Italy

    R. Ientile

  4. Department of Biological, Geological and Environmental Sciences, University of Catania, Catania, Italy

    M. Napoli

  5. Department of Drug Sciences, University of Catania, Catania, Italy

    A. Campisi & G. Li Volti

Authors
  1. V. Bramanti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. Tomassoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Grasso
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Bronzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Napoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Campisi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. G. Li Volti
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. R. Ientile
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. F. Amenta
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. R. Avola
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V. Bramanti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bramanti, V., Tomassoni, D., Grasso, S. et al. Cholinergic Precursors Modulate the Expression of Heme Oxigenase-1, p21 During Astroglial Cell Proliferation and Differentiation in Culture. Neurochem Res 37, 2795–2804 (2012). https://doi.org/10.1007/s11064-012-0873-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-012-0873-3

Keywords

Search

Navigation