Skip to main content
Log in

Visfatin Inhibits Apoptosis and Necrosis of Hippocampus CA3 Cells Following Transient Global Ischemia/Reperfusion in Rats

  • Published:
International Journal of Peptide Research and Therapeutics Aims and scope Submit manuscript

Abstract

Visfatin, a novel adipokine, is predominantly produced by visceral adipose tissue and it has been linked to a diverse variety of cellular processes and it is an important factor in cell apoptosis and survival. Cerebral ischemia causes loss of hippocampus pyramidal cells. In this study, we investigated the neuroprotective effects of visfatin in rats after global cerebral ischemia. Both common carotid arteries were occluded for 20 min followed by reperfusion. Saline as a vehicle and visfatin at doses of 100 ng were injected intracerebro-ventriculary at the time of cerebral reperfusion. Apoptosis and necrosis were assessed 96 h after ischemia. The results showed that treatment with visfatin significantly reduces apoptosis (P < 0.05) and necrotic cell death (P < 0.001) in hippocampal CA3 area, compared to the ischemia group. In conclusion, visfatin treatment, found for the first time in the present study, reduces hippocampus CA3 injuries after cerebral ischemia through preventing neuronal necrosis and apoptosis.

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

Similar content being viewed by others

References

  • Aboutaleb N, Kalalianmoghaddam H, Eftekhari S, Shahbazi A, Abbaspour H, Khaksari M (2014) Apelin-13 inhibits apoptosis of cortical neurons following brain ischemic reperfusion injury in a transient model of focal cerebral ischemia. Int J Pept Res Ther 20:127–132

    Article  CAS  Google Scholar 

  • Borradaile NM, Pickering JG (2009) Nicotinamide phosphoribosyltransferase imparts human endothelial cells with extended replicative lifespan and enhanced angiogenic capacity in a high glucose environment. Aging Cell 8:100–112

    Article  CAS  PubMed  Google Scholar 

  • Bułdak RJ, Bułdak Ł, Polaniak R, Kukla M, Birkner E, Kubina R, Kabała-Dzik A, Duława-Bułdak A, Żwirska-Korczala K (2013) Visfatin affects redox adaptative responses and proliferation in Me45 human malignant melanoma cells: an in vitro study. Oncol Rep 29:771–778

    PubMed  Google Scholar 

  • Cheng Q, Dong W, Qian L, Wu J, Peng Y (2011) Visfatin inhibits apoptosis of pancreatic β-cell line, MIN6, via the mitogen-activated protein kinase/phosphoinositide 3-kinase pathway. J Mol Endocrinol 47:13–21

    Article  CAS  PubMed  Google Scholar 

  • Dahl TB, Haukeland JW, Yndestad A, Ranheim T, Gladhaug IP, Damås JK, Haaland T, Løberg EM, Arntsen B, Birkeland KR (2010) Intracellular nicotinamide phosphoribosyltransferase protects against hepatocyte apoptosis and is down-regulated in nonalcoholic fatty liver disease. J Clin Endocrinol Metab 95:3039–3047

    Article  CAS  PubMed  Google Scholar 

  • Dahl TB, Holm S, Aukrust P, Halvorsen B (2012) Visfatin/NAMPT: a multifaceted molecule with diverse roles in physiology and pathophysiology. Annu Rev Nutr 32:229–243

    Article  CAS  PubMed  Google Scholar 

  • Dirnagl U, Iadecola C, Moskowitz MA (1999) Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 22:391–397

    Article  CAS  PubMed  Google Scholar 

  • Edwards JL, Vincent AM, Cheng HT, Feldman EL (2008) Diabetic neuropathy: mechanisms to management. Pharmacol Ther 120:1–34

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Florian C, Roullet P (2004) Hippocampal CA3-region is crucial for acquisition and memory consolidation in Morris water maze task in mice. Behav Brain Res 154:365–374

    Article  PubMed  Google Scholar 

  • Gheibi S, Aboutaleb N, Khaksari M, Kalalian-Moghaddam H, Vakili A, Asadi Y, Mehrjerdi FZ, Gheibi A (2014) Hydrogen sulfide protects the brain against ischemic reperfusion injury in a transient model of focal cerebral ischemia. J Mol Neurosci 54:264–270

  • Khaksari M, Aboutaleb N, Nasirinezhad F, Vakili A, Madjd Z (2012) Apelin-13 protects the brain against ischemic reperfusion injury and cerebral edema in a transient model of focal cerebral ischemia. J Mol Neurosci 48:201–208

    Article  CAS  PubMed  Google Scholar 

  • Kirino T, Tamura A, Sano K (1985) Selective vulnerability of the hippocampus to ischemia—reversible and irreversible types of ischemic cell damage. Prog Brain Res 63:39–58

    Article  CAS  PubMed  Google Scholar 

  • Kuroda S, Siesjö B (1996) Reperfusion damage following focal ischemia: pathophysiology and therapeutic windows. Clin Neurosci 4:199–212

    Google Scholar 

  • Lim SY, Davidson SM, Paramanathan AJ, Smith CC, Yellon DM, Hausenloy DJ (2008) The novel adipocytokine visfatin exerts direct cardioprotective effects. J Cell Mol Med 12:1395–1403

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mitani A, Andou Y, Kataoka K (1992) Selective vulnerability of hippocampal CA1 neurons cannot be explained in terms of an increase in glutamate concentration during ischemia in the gerbil: brain microdialysis study. Neuroscience 48:307–313

    Article  CAS  PubMed  Google Scholar 

  • Moskowitz MA, Lo EH, Iadecola C (2010) The science of stroke: mechanisms in search of treatments. Neuron 67:181–198

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nicholls DG, Ward MW (2000) Mitochondrial membrane potential and neuronal glutamate excitotoxicity: mortality and millivolts. Trends Neurosci 23:166–174

    Article  CAS  PubMed  Google Scholar 

  • Paxinos G, Watson C (2006) The rat brain in stereotaxic coordinates: hard cover edition. Academic press

  • Revollo JR, Grimm AA, Imai S-I (2007) The regulation of nicotinamide adenine dinucleotide biosynthesis by Nampt/PBEF/visfatin in mammals. Curr Opin Gastroenterol 23:164–170

    Article  CAS  PubMed  Google Scholar 

  • Rolo AP, Palmeira CM (2006) Diabetes and mitochondrial function: role of hyperglycemia and oxidative stress. Toxicol Appl Pharmacol 212:167–178

    Article  CAS  PubMed  Google Scholar 

  • Rongvaux A, Shea RJ, Mulks MH, Gigot D, Urbain J, Leo O, Andris F (2002) Pre-B-cell colony-enhancing factor, whose expression is up-regulated in activated lymphocytes, is a nicotinamide phosphoribosyltransferase, a cytosolic enzyme involved in NAD biosynthesis. Eur J Immunol 32:3225–3234

    Article  CAS  PubMed  Google Scholar 

  • Samal B, Sun Y, Stearns G, Xie C, Suggs S, McNiece I (1994) Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor. Mol Cell Biol 14:1431–1437

    PubMed Central  CAS  PubMed  Google Scholar 

  • Sharifi Z-N, Abolhassani F, Zarrindast MR, Movassaghi S, Rahimian N, Hassanzadeh G (2012) Effects of FK506 on hippocampal CA1 cells following transient global ischemia/reperfusion in Wistar rat. Stroke Res Treat. doi:10.1155/2012/809417

  • Simpkin JC, Yellon DM, Davidson SM, Lim SY, Wynne AM, Smith CC (2007) Apelin-13 and apelin-36 exhibit direct cardioprotective activity against ischemiareperfusion injury. Basic Res Cardiol 102:518–528

    Article  CAS  PubMed  Google Scholar 

  • Smith M-L, Auer R, Siesjö B (1984) The density and distribution of ischemic brain injury in the rat following 2–10 min of forebrain ischemia. Acta Neuropathol 64:319–332

    Article  CAS  PubMed  Google Scholar 

  • Wang P, Xu TY, Guan YF, Tian WW, Viollet B, Rui YC, Zhai QW, Su DF, Miao CY (2011) Nicotinamide phosphoribosyltransferase protects against ischemic stroke through SIRT1-dependent adenosine monophosphate–activated kinase pathway. Ann Neurol 69:360–374

    Article  CAS  PubMed  Google Scholar 

  • White BC, Sullivan JM, Degracia DJ, O’neil BJ, Neumar RW, Grossman LI, Rafols JA, Krause GS (2000) Brain ischemia and reperfusion: molecular mechanisms of neuronal injury. J Neurol Sci 179:1–33

    Article  CAS  PubMed  Google Scholar 

  • Zhang W, Xie Y, Wang T, Bi J, Li H, Zhang LQ, Ye SQ, Ding S (2010) Neuronal protective role of PBEF in a mouse model of cerebral ischemia. J Cereb Blood Flow Metab 30:1962–1971

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zhao Y, Liu XZ, Tian WW, Guan YF, Wang P, Miao CY (2014) Extracellular visfatin has nicotinamide phosphoribosyltransferase enzymatic activity and is neuroprotective against ischemic injury. CNS Neurosci Ther 20:539–547

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by a Grant (under the contract number 91052159) sponsored by the Iran National Science Foundation (INSF). The authors are very grateful to INSF for financial support. This article does not contain any studies with human or animal subjects performed by any of the authors.

Conflict of interest

Sohaila Erfani, Nahid Aboutaleb, Shahrbanoo Oryan, Nabi Shamsaei, Mehdi Khaksari, Hamid Kalalian-Moghaddam, Farnaz Nikbakht, declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mehdi Khaksari.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Erfani, S., Aboutaleb, N., Oryan, S. et al. Visfatin Inhibits Apoptosis and Necrosis of Hippocampus CA3 Cells Following Transient Global Ischemia/Reperfusion in Rats. Int J Pept Res Ther 21, 223–228 (2015). https://doi.org/10.1007/s10989-014-9449-1

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10989-014-9449-1

Keywords

Navigation