Induction of cell surface blebbing by increased cellular Pi concentration

Abstract

Cell surface blebbing is an early, reversible characteristic of anoxia described in several different cell types. Blebbing may lead to the formation of large terminal blebs, and ultimately cell death upon rupture of the membrane. In the present work, evidence is presented indicating that Pi may be the immediate mediator of cell surface blebbing: (1) cell surface blebbing can be induced in normoxic Ehrlich ascites tumour cells by a high extracellular concentration of Pp leading to an increase in the cellular Pi concentration; (2) anoxia induces sustained elevation of the cellular Pi concentration and (3) cell surface blebbing during anoxia is reversed upon reoxygenation, and the disappearance of blebbing depends on the decrease in cellular Pi concentration. The rate of disappearance of blebs may be enhanced by the simultaneous addition of adenine and inosine to the growth medium. This leads to a decrease in cellular Pi concentration and to an almost complete restoration of the cellular ATP concentration. It is suggested that Pi is an important mediator of anoxia induced cell damage.

Tumour cell blebbing and extracellular vesicle shedding: key role of matrikines and ribosomal protein SA

“…[47][48][49] Cells undergo blebbing after exposure to substance P/neurokinin-1 receptor complex, H 2 O 2 , ATP and Pi. [50][51][52][53][54][55] We demonstrated for the first time that ECM degradation products modify cancer cell morphology by generating a blebbing phenomenon in absence of FCS, leading to extracellular vesicle shedding. During tumour progression, elastin is cleaved by many proteinases secreted locally or circulating in serum.…”

Phosphate Is a Specific Signal for ATDC5 Chondrocyte Maturation and Apoptosis-Associated Mineralization: Possible Implication of Apoptosis in the Regulation of Endochondral Ossification

“…Whether increase in intracellular Pi concentration results from an active Pi transport from the ECM or from intracellular Pi generation is not yet fully understood. On one hand, chondrocytes highly express sodium‐dependent (37,38) and ‐independent (39) Pi transporters that could account for high intracellular Pi levels; on the other hand, this high Pi content and the low ATP/Pi ratio reported in vivo (13) could result from hypoxic injury as it was reported in other cell types (40) . In the poorly vascularized growth plate, the most hypoxic chondrocytes are localized in the hypertrophic zone (8) .…”

“…On one hand, chondrocytes highly express sodium-dependent (37,38) and -independent (39) Pi transporters that could account for high intracellular Pi levels; on the other hand, this high Pi content and the low ATP/Pi ratio reported in vivo (13) could result from hypoxic injury as it was reported in other cell types. (40) In the poorly vascularized growth plate, the most hypoxic chondrocytes are localized in the hypertrophic zone. (8) In the present study, we sought to explore the relationship between chondrocyte maturation and cartilage mineralization induced by Pi using the ATDC5 in vitro model of endochondral ossification.…”

A New Possible Function for Placental Pericytes

“…Apoptosis is not, however, the only cause of formation of cell blebs, they can also be formed as a response to noxious stimuli such as hypoxia, metabolic poisoning, disturbances in extracellular thiol and calcium ion homeostasis, high concentrations of free radicals [Jewell et al, 1982] and increased cellular inorganic phosphate P i concentration [Marcussen, 1996]. In HeLa cells, necrotic blebs differ from apoptotic blebs in that they do not retract and are associated more with cell swelling than shrinkage.…”