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LVV-hemorphin-4 modulates Ca2+/calmodulin-dependent pathways in the immune system by the same mechanism as in the brain

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Abstract

The effect of synthetic LVV-hemorphin-4 (LVV-H4) on human blood and tonsils lymphocytes total phosphatase activity was studied by a spectrofluorimetric assay using 4-methylumbelliferyl phosphate (4-MUP) as a substrate. It has been established that LVV-H4 at concentrations of 10−9 to 10−7 M induces the inhibition of human blood (12–24%) and tonsils (42–45%) lymphocytes total phosphatase activity as 1 mM EGTA. The same peptide at concentrations of 10−5 to 10−4 M induces activation of human blood (48–57%) and tonsils (20–25%) lymphocytes total phosphatase activity. LVV-H4 is able to neutralize the inhibitory effect of calmodulin (CaM) antagonist and calcineurin inhibitor trifluoperazine (TFP) on human blood lymphocyte total phosphatase activity. It is suggested that a dose-dependent activation/inhibition of lymphocytes total phosphatase activity is due to activation/inhibition of lymphocyte calcineurin activity. Using enzyme-linked immunosorbent assay (ELISA) it was found that LVV-H4 neutralized the inhibitory effect of cyclosporin A (CsA) and TFP on interleukin-2 (IL-2) synthesis by activated blood lymphocytes. LVV-H4 also affects the lymphocytes proliferation, suppressed in pathophysiological condition, and restores their function by enhancement of DNA synthesis, as determined by measuring of [3H] thymidine incorporation into lymphocytes. It has been proposed that CaM is an essential component in starting up the molecular mechanism of hemorphins action and that calcineurin is a key enzyme underlying the molecular mechanism of hemorphins action on the brain and immune system.

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Authors and Affiliations

  1. H. Buniatian Institute of Biochemistry of the National Academy of Sciences of the Republic of Armenia (RA), 375014, Yerevan, RA

    Nina Barkhudaryan & Tadevos Gyulbayazyan

  2. A. Mikaelyan Institute of Surgery of the Ministry of Health RA, 375052, Yerevan, RA

    Spartak Gambarov, Tadevos Gyulbayazyan & Karine Nahapetyan

Authors
  1. Nina Barkhudaryan
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  2. Spartak Gambarov
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  3. Tadevos Gyulbayazyan
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  4. Karine Nahapetyan
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Correspondence to Nina Barkhudaryan.

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Barkhudaryan, N., Gambarov, S., Gyulbayazyan, T. et al. LVV-hemorphin-4 modulates Ca2+/calmodulin-dependent pathways in the immune system by the same mechanism as in the brain. J Mol Neurosci 18, 203–210 (2002). https://doi.org/10.1385/JMN:18:3:203

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  • DOI: https://doi.org/10.1385/JMN:18:3:203

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