The Role of Microsomal Galactose-Specific Lectins from Prostate Tissues in Gland Peroxidation

Author: Elene Davitashvili
Keywords: Microsomal Lectins, Lipid Peroxidation, Malondialdehyde, Prostate Gland Diseases
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Studies about physiological and biological properties of endogenous lectins have become a prominent issue in the recent years. Lectins are nonimmune proteins that selectively recognize and reversibly binding to the terminal or subterminal carbohydrate determinants of glycoconjugates with no enzymatic activity; thus forming non-covalent bonds. Lectins participate in the regulation of many crucial biological processes, such as cell recognition, cellular differentiation, adhesion, signal transduction, embryogenesis, modulation of immune responses, fertilization, membrane transport, apoptosis, modulation of enzymatic activity, and cell division. Number of endogenous and exogenous lectins promote synthesis of reactive oxygen species (ROS). Some of endogenous lectins are characterized by mitogenic activity and participate in tumor progression and metastasis. Galactose-specific lectins are proteins with multifunctional properties, modulate cancerogenesis multistep process, and induce the remarkable generation of intracellular hydrogen peroxide. Considering the fact that prostate cancer is the one of the most frequently diagnosed malignancy in males and the second leading cause of cancer-related death among men, our efforts have been concentrated on understanding the role of endogenous lectins from prostate tissue, in the progression of gland tumor. Relatively little is known about molecular events that underlie the development and progression of prostate cancer. Its’ known that prostate cancer is a disease associated with aging and oxidative stress (a shift in prooxidant-antioxidant balance), which is also commonly associated with the age. Microsomes play a significant role in tumorigenesis by production of free radicals in prostate microsomes. Lectins are one of the important chemical agents that induce ROS production and modulate cancerogenesis multistep process, they induce generation of large amount of intracellular hydrogen peroxide molecules at an early phase, thus resulting in apoptotic death of cancer cells. There is less information about the microsomal lectins and their role in the prostate diseases. On one hand, a scarce data is available about the microsomal lectins in the liver and the brain cells. On the other hand, more information has been reported about the biological role of lectins isolated from the endoplasmic reticulum neoplasicand atypical tissue cells (calreticulin and calnexin) of prostate. Take into consideration the afore-mentioned the aim of the present study was: 1. To purification and investigation of certain properties of microsomal galactose-specific lectins from prostate post-operation tissues of men with different diagnosis; 2. Comparative analysis of their properties; 3. An investigation the role of prostate microsome galactose-specific lectins in vitro model experiments (bovine liver tissue cells) system on some aspects of peroxidation processes and hydrogen peroxide production, as one of the causes of tumor genesis. and 4. Understanding of the role of prostate microsomal galactose-specific lectins in peroxidation processes. In this data we aim to investigate the effects of galactose-specific lectins isolated from the microsomal fraction of tissues with different diagnosis on some aspects of peroxidation processes The beta-galactose-specific lectins were isolated from the microsomal fraction of prostate tissues with different diagnosis: benign prostate hyperplasia with low-grade intraepithelial neoplasia (BPH/LGPIN), high grade intraepithelial neoplasia (HGPIN), atypical adenomatous hyperplasia (AAH) and adenocarcinoma (PC).The molecular weight of isolated lectins (60kDa) found to be similarand and all the lectins tested proved positive to the Schiff’s reagent, which indicate to their glycoprotein nature. Their biological effects are different. The lectin from BPH/LGPIN tissue microsomes did not change the amount of malondyaldehyde (MDA), while the lectin from HGPIN, AAH and PC tissue microsomes induced increasing production of MDA. The lectins from all sources increase the amount of H2O2 in time-dependent manner. These effects are mediated by galactose binding domain of the lectins as are completely abolished by the inclusion of galactose. We proposed that one of the reasons of the revealed changes in the biological properties of lectins induced by alteration in the lectin‘s carbohydrate moiety structure. There is evidence that the changes of biological properties of prostate galactose-specific lectins are functionally related to development of the metabolic changes during prostate pathogenesis. In view of endoplasmic reticulum in many ways involved in carcinogenesis, we proposed the possible way, the released galactose-specific lectins from damaged microsomes enhances further transformation of prostate tissue by induction of MDA production and generation of free H2O2.