Elsevier

Brain Research

Volume 743, Issues 1–2, 16 December 1996, Pages 362-365
Brain Research

Short communication
Effect of systemic zinc administration on delayed neuronal death in the gerbil hippocampus

https://doi.org/10.1016/S0006-8993(96)01112-2Get rights and content

Abstract

The divalent cation zinc has been reported to possess several physiological properties such as blocking apoptotic cell death through an inhibitory effect on Ca2+-Mg2+ endonuclease activity, or modulating the neurotoxicity via glutamate receptor subtypes. In the present study, we investigated the effect of peripherally injected zinc on delayed neuronal death seen in the hippocampus after transient global ischemia, in order to elucidate a possible beneficial role on zinc in ischemic neuronal cell death. Forty-five adult Mongolian gerbils of both sexes underwent transient bilateral clipping of the common carotid arteries for 3 min. In the pretreated animals, ZnCl2 (20 mg/kg) was injected subcutaneously once, 1 h before ischemia (superacute group; n=6) or twice at 24 and 48 h before ischemia (subacute group; n=14). Histological survey was carried out 3 days later by in situ DNA fragmentation method and 4 days later by hematoxylin-eosin staining by semiquantatively counting dead neurons in the CA1 sector. Subacute zinc pre-administration significantly reduced the nuclear damage and subsequent neuronal death; however, superacutely pre-administered zinc did not protect hippocampal neurons against ischemia but it did not aggravate the effect of ischemia, either. The present study suggested that transfer of exogenous zinc into the intracellular space is required for neuroprotection, presumably via the anti-endonuclease activity.

Section snippets

Acknowledgements

This work was supported by a research grant for cardiovascular diseases from the Japanese Ministry of Health and Welfare and was in part supported by Health Science Research Grants by the Ministry of Health and Welfare of Japan. We also wish to express our thanks to Dr. H. Naritomi (National Cardiovascular Center, Osaka, Japan) who gave us supports for experimental preparations in this study and Ms. M. Shimomura and R. Manabe for their secretarial assistance.

References (20)

  • Bonfoco, E., Krainc, D., Ankarcrona, M., Nicotera, P. and Lipton, S.A., Apoptosis and necrosis: Two distinct events...
  • Choi, D.W., Calcium: still center-stage in hypoxic-ischemic neuronal death, Trends Neurosci., 18 (1995)...
  • Cohen, J.J. and Duke, R.C., Glucocorticoid activation of a calcium-dependent endonuclease in thymocyte nuclei leads to...
  • Frederickson, C.J., Hernandez, M.D. and McGinty, J.F., Translocation of zinc may contribute to seizure-induced death of...
  • Gavrieli, Y., Sherman, Y. and Bensasson, S.A., Identification of programmed cell death in situ via specific labeling of...
  • Kitagawa, K., Matsumoto, M., Oda, T., Niinobe, M., Hata, R., Handa, N., Fukunaga, R., Isaka, Y., Kimura, K., Maeda, H.,...
  • Koh, J., Suh, S.W., Gwag, B.J., He, Y.Y., Hsu, C.Y. and Choi, D.W., The role of zinc in selective neuronal death after...
  • Li, H. and Buchan, A.M., Treatment with an AMPA antagonist 12 hours following severe normothermic forebrain ischemia...
  • Linnik, M., Zobrist, R.H. and Hatfield, M.D., Evidence supporting a role for programmed cell death in focal cerebral...
  • MacManus, J.P., Buchan, A.M., Hill, I.E., Rasquinha, I. and Preston, E., Global ischemia can cause DNA fragmentation...
There are more references available in the full text version of this article.

Cited by (67)

  • The critical role of the zinc transporter Zip2 (SLC39A2) in ischemia/reperfusion injury in mouse hearts

    2019, Journal of Molecular and Cellular Cardiology
    Citation Excerpt :

    Zinc is essential for the structure and function of many proteins [1] and has been demonstrated to be cytoprotective [2,3].

  • The effect of zinc acexamate on oxidative stress, inflammation and mitochondria induced apoptosis in rat model of renal warm ischemia

    2018, Biomedicine and Pharmacotherapy
    Citation Excerpt :

    Moreover, it has been shown that apoptosis was increased in different Zn deprivation models [53,54]. Indeed, Zn supply prevented apoptosis following transient forebrain ischemia [55] and Zn chelation increased caspase-3 activity [56]. In our study, the significant decrease of the pro-apoptotic protein caspase-9 confirmed the protective role of ZAC at 10 mg/kg against apoptosis.

  • Zinc pyrithione inhibits caspase-3 activity, promotes ErbB1-ErbB2 heterodimerization and suppresses ErbB2 downregulation in cardiomyocytes subjected to ischemia/reperfusion

    2015, Journal of Inorganic Biochemistry
    Citation Excerpt :

    The influence of zinc on apoptosis is a well known phenomenon [30]. In both in vitro and in vivo models, zinc supplementation prevents apoptosis induced by a variety of agents [31,32]. Moreover, cells grown under conditions of zinc deficiency will undergo spontaneous apoptosis [33,34].

  • Expression of executioner procaspases and their activation by a procaspase-activating compound in chronic lymphocytic leukemia cells

    2015, Blood
    Citation Excerpt :

    One key physiological regulator that maintains the executioner caspase in an inactive procaspase configuration is its inhibition by labile intracellular zinc.4 After the first demonstration that addition of zinc ion specifically inhibited caspase-3 cleavage activity and caspase-3–mediated apoptosis,5 a series of reports showed that addition of zinc increased cytoprotection6,7 and deprivation of zinc ion induced apoptosis.8-10 These findings provided an impetus to create small molecules to chelate the intracellular zinc to activate caspases.11

  • The role of zinc in immunity and inflammation

    2013, Diet, Immunity and Inflammation
View all citing articles on Scopus
View full text