Fish and Apoptosis: Molecules and Pathways

Abstract

Apoptosis is a genetically controlled and evolutionarily conserved form of active cell death, albeit with an increase in complexity with continuing development. A high conservation at the functional and molecular level has been described between the players of the apoptotic machinery in invertebrates (Caenorhabditis elegans and Drosophila) and mammals. However, fish represent an excellent and advantageous model for the study of vertebrate development and disease, bridging the gap between the C. elegans/Drosophila and mouse/human models. Moreover, contrary to C. elegans and Drosophila, fish can be used for studying the development and function of vertebrate-specific organs and have a fully developed immune system similar to that of mammals. Last but not less important, both the environment and human health will obviously gain by using the knowledge generated through the use of fish models, for developing better prophylactic and therapeutic measures with impact on the aquaculture industry. In the present article, structural and functional data on the most important apoptosis related molecules, namely death-receptor, Bcl-2 and caspase families, and mechanisms are reviewed. The data point to the existence in fish of apoptotic pathways equivalent to those of mammals, making fish useful animal models for studying apoptosis, which may have great applicability for the advance of the knowledge on the role of apoptotic cell death in human apoptosis-related disorders as well as in pharmaceutical design.

Expression analysis of immune response genes in fish epithelial cells following ranavirus infection

“…In addition to their various roles in the innate immune response, TNF-a and IL-1b have been associated with the induction of apoptosis. The binding of TNF-a to a specific cell surface receptor, TNFR1, initiates the signalling pathway leading to apoptosis [39]. Furthermore, both TNF-a and IL-1b stimulate the production of another antiviral cytokine, IFN-g, which is a potent mediator of apoptosis [40,41].…”

The zebrafish as a model organism for the study of apoptosis

“…Fish models may provide unique advantages for the study of apoptosis [168,169]. Zebrafish and other teleost species are useful for studying apoptotic cell death occurring not only during embryonic development but also in response to a variety of external stimuli including changes in oxygen availability, osmotic stress, high and low temperatures, and exposure to toxins.…”

Zebrafish as a model system for biomedical studies

“…Индукция апоптоза является важным механизмом эффективной противоопухолевой терапии [48]. Установлено, что процесс апоптоза у зебрафиш и млекопитающих имеет много общего [49]. Так у зебрафиш идентифицировано большинство генов, связанных с апоптозом, семь каспаз (каспазы-2, -3, -4, -6, -8, -9, -13), четыре ингибитора апоптоза, 10 участвующих в процессе апоптоза киназ, факторы транскрипции и многие другие молекулы, связанные с гибелью клетки [16,49].…”

“…Установлено, что процесс апоптоза у зебрафиш и млекопитающих имеет много общего [49]. Так у зебрафиш идентифицировано большинство генов, связанных с апоптозом, семь каспаз (каспазы-2, -3, -4, -6, -8, -9, -13), четыре ингибитора апоптоза, 10 участвующих в процессе апоптоза киназ, факторы транскрипции и многие другие молекулы, связанные с гибелью клетки [16,49]. Для идентификации гибнущих клеток используются различные методы, в том числе, прижизненное окрашивание акридиновым оранжевым; иммунологический метод выявления активированной каспазы-3; а также окрашивание трипановым синим для выявления целостности клеточной мембраны.…”