MOLECULAR APOPTOSIS MECHANISMS WITH UNDERLYING EXPERIMENTAL ACUTE LUNG INJURY
Background. Current data suggest systemic autoimmune activation in the pathogenesis of bronchopulmonary diseases. The imbalance in the system of pro- and anti-inflammatory cytokines is very important in immunopathogenesis.
Objective. The aim of our research was to determine the caspase-3 rate in the dynamics of experimental acute lung injury and to study the relationship between their level and the number of cells carrying membrane binding TNF receptor type 1 to define the main mechanisms of cell death.
Results. The analysis of the results of caspase-3 rate in lung homogenate showed that this cysteine proteinase was uniformly increasing in all experimental groups during simulating of ALI induced by administration of hydrochloric acid (p<0.001). When comparing the results of caspase course of apoptosis it was defined that, despite the progressive increase in caspase-3 rate in lung homogenate, cysteine proteinase rate in plasma did not change. The receptor mechanism of apoptosis was studied by establishing correlation relationships with the number of cells carrying membrane binding TNF type 1 (TNF-R1) receptor. A strong positive correlation relationship between the number of neutrophils with TNF-R1 and caspase-3 rate in lungs of all research groups was determined.
Conclusions. The implementation of neutrophils death by apoptosis is caused by change of activity of caspase cascade effector components, such as caspase-3, in cases of ALI induced by intratracheal administration of hydrochloric acid. One of the potential mechanisms responsible for the activation of caspase course is excessive generation of active forms of oxygen and increase in the number of neutrophils carrying membrane binding TNF receptor type 1.
Mitchell RS, Martin TR. Lung Cytokines and ARDS. Chest 1999; 116: 2–8.
Schneider-Brachert W, Tchikov V, Neumeyer J et al. Compartmentalization of TNF receptor 1 signaling; internalized TNF receptosomes as death vesicles. J. Immunity 2004; 21 (3): 415–428.
MacEwan DJ. TNF ligand and receptors – a matter of life and death. British Jour. of Pharm 2002; 135: 855–875.
Roth Z’graggen B, Tornic J, Miller-Edenborn B et al. Acute lung injury: apoptosis in effector and target cells of the upper and lower airway compartment. Clinical and Experimental Immunology 2010; 161: 324–331.
Kaminski M, Kiebling M, Suss D et al. Novel Role for Mitochondria: Protein Kinase Cθ-Dependent Oxidative Signaling Organelles in Activation-Induced T-Cell Death. Mol Cell Biol 2007; 27 (10): 3625-3639.
Hlumcher FS, Berezniakov YH, Reshedko HK. 1 Ukraynskyi konhress po voprosam antymykrobnoi terapyy: sobytye dlia otechestvennoho zdravookhranenyia. Zdorovia Ukrainy 2007; 2 (1): 16–18.
European convention for the protection of vertebrate animals used for experimental and other scientific purposes. Council of Europe. Strasbourg 1986; 123: 52.
Hudyma AA, Marushchak MI, Habor HH, Kulitska MI. Patohenetychna rol neitrofilnykh hranulotsytiv u rozvytku hostroho urazhennia lehen. Bukovynskyi medychnyi visnyk 2011; 3: 82–86.
Bonomini M, Dottori S, Amoroso L et al. Increased platelet phosphatidylserine exposure and caspase activation in chronic uremia. J Thromb Haemost 2004; 2(8): 1275–1281.
Chasovskykh NIu. Rol proteynkynaz JNK y r38 v rehuliatsyy apoptoza mononuklearnykh leikotsytov krovy pry okyslytelnom stresse. Biulleten sybyrskoi medytsyny 2008; 3: 38–43.
Pasechnyk AV, Frolov VA. Apoptoz neitrofylov kak parametr vospalytelnoi reaktsyy pry patolohyy. Vestnyk RUDN. Seryia Medytsyna 2004; 25 (1): 103.
Mann DL. Recent insights into the role of tumor necrosis factor in the failing heart. Heart Fail Rev 2001; 6(2): 71–80.
Hryshchuk LA, Marushchak MI. Dynamika perekysnoho okysnennia lipidiv ta antyoksydantnoho zakhystu v shchuriv za umov hostroho urazhennia lehen. Tuberkuloz, lehenevi khvoroby, VIL-infektsiia 2011; 2 (05): 16–20.
Myshunina TM, Tronko MD. Osnovni molekuliarni mekhanizmy apoptozu ta yikh porushennia pry kantserohenezi shchytopodibnoi zalozy (ohliad literatury). Zhurn AMN Ukrainy 2006; 12 (4): 611–633.
Raikhlyn NT, Raikhlyn AN. Rehuliatsyia y proiavlenye apoptoza v fyzyolohycheskykh uslovyiakh y v opukholiakh. Vopr onkol 2002; 48 (2): 159–171.
Myshunina TM, Kalinichenko OV, Tronko MD, Zurnadzhy LIu. Kharakterystyka zmin pronyknosti membran mitokhondrii z tkanyny papiliarnykh kartsynom shchytopodibnoi zalozy ta z yii tkanyny za invazii pukhlynnykh klityn. Zhurn AMN Ukrainy 2010; 16 (1): 5–22.
Chopra M, Reuben JS, Sharma AC. Acute Lung Injury: Apoptosis and Signaling Mechanisms. -Experimental Biology and Medicine 2009; 234: 361–371.
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