Growth factors as survival factors: Regulation of apoptosis

Abstract

SummaryApoptosis is now widely recognized as a common form of cell death and represents a mechanism of cell clearance in many physiological situations where deletion of cells is required. Peptide growth factors, initially characterised as stimulators of cell proliferation, have now been shown to inhibit death in many cell types. Deprivation of growth factors leads to the induction of apoptosis, i.e. condensation of chromatin and degradation in oligonucleosomesized fragments, formation of plasma and nuclear membrane blebs and cell fragmentation into apoptotic bodies which can be taken up by neighbouring cells. Here we discuss the mechanism(s) by which growth factors may inhibit apoptosis. Apoptosis: an overviewOften referred to as programmed cell death, apoptosis has been extensively reported in the scientific literature through morphological studies in many tissues where death was taking place as a consequence of a physiological phenomenon (reviewed in ref. 1). In these studies the presence of scattered single cells with highly condensed chromatin has been one of the parameters indicating the presence of apoptotic cell death(2). In a later phase the chromatin appears to be distributed into sub-cellular structures called apoptotic bodied3).However, apoptosis is not only observed in the balanced situation of physiological tissue turnover but also in the elimination of specific cell subsets that occurs in embryogenesis, for instance in the embryonic development of the intestine and nervous system and in the regression of female sexual organs in the male(4). Apoptosis has also been implicated as the mechanism of cell elimination during tissue regression in metamorph~sis(~). Apoptotic cells have also been observed during tumour growth and regression. Thus, for example, apoptotic bodies of epithelial cell origin were described during development of squamous cell carcinoma(6) and kinetics studies have demonstrated waves of apoptosis during sarcoma growth(7). Therefore, during tumour growth some cells, perhaps those deprived of growth factors, undergo apoptosis. When tumours are treated with chemotherapy, apoptosis is responsible for at least some of the cell deaths which ensue(*).There are further experimental modulations of tissues where cell death is induced and apoptosis is observed. Regression of hyperplastic organs such as the liver or kidneys after lead poisoning is accompanied by the appearance of apoptotic celld9). Apoptosis is observed in the rat prostate after repeated withdrawal of testosterone stimulation(10), in rat liver after removal of tumour promoters(l]), in keratinocytes after UV irradiation(12) and in neuronal cells following glutamate treatment(13).Because apoptotic cells are rapidly, and specifically, engulfed in vivo by neighbouring cells(14) in order to keep cell debris to a minimum and to allow shrinkage of a tissue without disruption of its basic architecture, these morphological tissue studies probably greatly underestimate the number of deaths occurring. Indeed, it has been proposed that man...

IL-33/ST2 axis promotes mast cell survival via BCLXL

“…Human MC were cultured from human skin in serum-free medium containing SCF (38). Growth factor withdrawal is a standard model of apoptosis induction (39). Accordingly, MC (1 × 10 5 /mL) were treated with or without IL-33 (10 ng/mL) in the presence or absence of SCF for 3 d. The percentage of apoptotic MC [Annexin V + propidium iodide (PI) − ] was measured using flow cytometry.…”

Chondrocyte apoptosis in endochondral ossification of chick sterna

“…In contrast apoptosis is characterized by the presence of a condensed cell morphology with intact cell membranes (for reviews see Kerr and Harmon, 1991;Wyllie, 1992) and by fragmentation of DNA, in most cases, to nucleosoma1 units of multiples of approximately 180 base pairs (Wyllie, 1980). Apoptosis occurs in response to a variety of stimuli including growth factor withdrawal (Raff, 1992;Collins et al, 1994)) DNA damage (Lowe et al, 1993), and viral infection (Haecker and Vaux, 1994;White and Gooding, 1994). Apoptosis also occurs dur-ing the process of tissue morphogenesis, as classically seen in resorption of interdigital webbing in limb development (Hinchliffe and Ede, 1973).…”

Estudio de los factores materno-embrionario que determinan la fertilidad y prolificidad en una línea de conejo seleccionada por velocidad de crecimiento

“…De hecho, tanto TGF-β2 como VEGF y los receptores erbB están relacionados con la diferenciación del trofoblasto (Pidoux et al, 2007). El gen erbB participa en la activación específica intracelular de vías de señalización para el control de la proliferación celular, diferenciación y prevención de la apoptosis (Collins et al, 1994).…”

“…Estos resultados podrían explicar en parte, el hecho de que la expresión de los transcritos VEGF e Ifn-γ también sea similar en blastocistos de ambas líneas. De la misma forma, la expresión de factores de crecimiento como el TGF-β2, esencial para la implantación embrionaria y erbB a través de su receptor erbB3, relacionado con la activación de la señal que controla la proliferación celular, diferenciación y que previene la apoptosis (Collins et al, 1994;Kamijo et al, 1998;Klonish et al, 2001;Paria et al, 2001), han presentado similares niveles de expresión tanto en blastocistos como en endometrio de ambas líneas. Estos resultados podrían explicar las similares pérdidas preimplantacionales (hasta el día 6 de gestación) en ambas líneas, pero no las diferencias en las pérdidas hasta el día 12 y hasta el parto.…”

“…Los factores de crecimiento epidérmico (EGFs) y sus receptores (erbBs) se expresan en las células tanto del tracto reproductivo materno como del embrión (Dadi et al, 2009). La principal función de estas moléculas durante el desarrollo temprano embrionario es activar señales de mecanismos específicos intracelulares para el control de la proliferación celular, diferenciación y prevención de la apoptosis (Collins et al, 1994).…”