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Effect of melatonin treatment on AKT1 and P38 protein kinases expression in thymic and splenic lymphocytes
Author(s) -
Luzikova Elena,
Sergeeva Valentina,
Valentina Gordova N.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.972.11
Subject(s) - melatonin , spleen , red pulp , white pulp , p38 mitogen activated protein kinases , kinase , medicine , biology , marginal zone , endocrinology , antibody , protein kinase a , immunology , b cell , microbiology and biotechnology
Melatonin modulates the wide spectrum of physiological functions in lymphoid tissues. Several studies described the involvement of protein kinases (P38 and AKT1) in signaling pathways of many biological mechanisms such as cell differentiation, proliferation, apoptosis and selection. Little is known about the effect of melatonin on AKT1 and P38 protein kinases expression in lymphoid organs. This study checked the log‐time effect of melatonin on protein kinases Р38 and AKT1 expression in thymic and splenic lymphocytes of two months old male mice. The animals were divided in two groups: the control group got standardized drinking water ad libitum . The experimental group received ad libitum the same water containing 4 mg/liter melatonin (“Melaxen” Unipharm, Inc., US) for 28 days. Isolated thymus and spleen were embedded in paraffin and immunostained with antibodies against the P38 and AKT1. Images were analyzed using light microscope MIKMED 5. Melatonin treatment resulted in reduction of Р38 expression in cortical (CS) and medullary substance (MS) of thymic lobules in 1.7 (p ≤ 0. 001) and 1.6 (p ≤ 0.0001) times respectively. In spleen of control animals the P38‐positive cells were detected in red pulp, subcapsular zone, lymphoid nodules and marginal sinuses. Administration of melatonin reduced the P38‐positive cell number in red pulp in 1.3 times (p ≤ 0. 001) and in subcapsular zone in 7.4 times (p ≤ 0.0001), but up‐regulate in marginal sinuses in 4.6 times (p ≤ 0. 001). In spleen's white pulp the number of Р38‐positive cells was 3.3 (p ≤ 0. 001) higher in comparison with control. In thymocytes of CS and MS of thymic lobules from control animals AKT1 kinase was expressed intracellular (inactive form), and on plasma membrane (active form). The first type of cells was detected mostly in the CS of lobules. The second type ‐ in the subcapsular zone of the CS and in the MS. Administration of melatonin resulted in increasing number of thymocytes per field of view in CS in 4.2 times (p ≤ 0. 001), but the AKT1 expression in thymocytes plasma membrane was down‐regulates. The common number of AKT1 positive cells in subcapsular zones of thymic lobules was reduced. The immunoreactive signal of AKT1 expression in spleen shows the evenly weak distribution of kinase, especially in marginal zones of lymphoid nodules. Melatonin administration leads to the increasing number of lymphoid nodules in 3.5 times (r ≤ 0.001), up‐regulation of AKT1 expression in lymphocytes of nodules and reduction of AKT1 expression in the subcapsular zone of red pulp. Melatonin‐induced enhancement of lymphocytes proliferation in the thymus and spleen is accompanied by decreasing of Р38 and AKT1 expression in thymus and up‐regulation of these kinases in spleen.