Serum Proteases Potentiate BMP-Induced Cell Cycle Re-entry of Dedifferentiating Muscle Cells during Newt Limb Regeneration

The reported effects of alterations in Na-H exchange activity on mitogenesis are variable and appear dependent on the cell type examined. We examined the effects of reductions in ethylisopropylamiloride (EIPA)-sensitive pH-regulating mechanisms including Na-H exchange and alterations in intracellular pH (pHi) on the growth characteristics of rat aortic smooth muscle cells (RASM) cultured in serum-containing bicarbonate-buffered medium. Exposure of RASM replicating in bicarbonate-containing medium to the Na-H exchange inhibitors EIPA, dimethylamiloride (DMA), or amiloride (A) attenuated their replication rate. The order of potency of the inhibitors (EIPA greater than DMA much greater than A) was similar to their documented effects on Na-H exchange activity and to their order of potency for inhibiting recovery from CO2-induced acidosis in these cells. Reductions in pHi induced by lowering extracellular pH also attenuated the incorporation of [3H]-thymidine into DNA, while increases in pHi were associated with an acceleration in the rate of incorporation of [3H]thymidine into DNA. The effects of the Na-H exchange inhibitors on RASM replication were due to a reduction in the ability of the smooth muscle cells to enter the S phase of the mitotic cell cycle. This appeared predominantly the consequence of effects late within the G1 phase of the cell cycle. Concentrations of EIPA that markedly reduced the ability of RASM to enter S phase and to replicate also attenuated the increase in protein synthesis occurring 6-8 h after exposure to serum.(ABSTRACT TRUNCATED AT 250 WORDS)

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Exogenous ATP induces a limited cell cycle progression of arterial smooth muscle cells

AJP Cell Physiology ◽

10.1152/ajpcell.1993.264.4.c783 ◽

1993 ◽

Vol 264 (4) ◽

pp. C783-C788 ◽

Cited By ~ 46

Author(s):

R. Malam-Souley ◽

M. Campan ◽

A. P. Gadeau ◽

C. Desgranges

Keyword(s):

Cell Cycle ◽

Smooth Muscle ◽

Smooth Muscle Cells ◽

Cell Cycle Progression ◽

Mrna Level ◽

Muscle Cells ◽

Arterial Smooth Muscle ◽

Cycle Progression ◽

Arterial Smooth Muscle Cells ◽

Cycle Dependent

Because exogenous ATP is suspected to influence the proliferative process, its effects on the cell cycle progression of arterial smooth muscle cells were studied by investigating changes in the mRNA steady-state level of cell cycle-dependent genes. Stimulation of cultured quiescent smooth muscle cells by exogenous ATP induced chronological activation not only of immediate-early but also of delayed-early cell cycle-dependent genes, which were usually expressed after a mitogenic stimulation. In contrast, ATP did not increase late G1 gene mRNA level, demonstrating that this nucleotide induces a limited cell cycle progression of arterial smooth muscle cells through the G1 phase but is not able by itself to induce crossing over the G1-S boundary and consequently DNA synthesis. An increase in c-fos mRNA level was also induced by ADP but not by AMP or adenosine. Moreover, 2-methylthioadenosine 5'-triphosphate but not alpha, beta-methyleneadenosine 5'-triphosphate mediated this kind of response. Taken together, these results demonstrate that extracellular ATP induces the limited progression of arterial smooth muscle cells through the G1 phase via its fixation on P2 gamma receptors.

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Cell cycle controls and the role of nerves and the regenerate epithelium in urodele forelimb regeneration: possible modifications of basic concepts

Biochemistry and Cell Biology ◽

10.1139/o87-097 ◽

1987 ◽

Vol 65 (8) ◽

pp. 739-749 ◽

Cited By ~ 17

Author(s):

Roy A. Tassava ◽

David J. Goldhamer ◽

Bruce L. Tomlinson

Keyword(s):

Cell Cycle ◽

Monoclonal Antibody ◽

Limb Regeneration ◽

Blastema Formation ◽

Basic Concepts ◽

Regenerate Epithelium ◽

Early Wound ◽

Skin Epidermis ◽

Wound Epithelium

Data from pulse and continuous labeling with [3H]thymidine and from studies with monoclonal antibody WE3 have led to the modification of existing models and established concepts pertinent to understanding limb regeneration. Not all cells of the adult newt blastema are randomly distributed and actively progressing through the cell cycle. Instead, many cells are in a position that we have designated transient quiescence (TQ) and are not actively cycling. We postulate that cells regularly leave the TQ population and enter the actively cycling population and vice versa. The size of the TQ population may be at least partly determined by the quantity of limb innervation. Larval Ambystoma may have only a small or nonexisting TQ, thus accounting for their rapid rate of regeneration. Examination of reactivity of monoclonal antibody WE3 suggests that the early wound epithelium, which is derived from skin epidermis, is later replaced by cells from skin glands concomitant with blastema formation. WE3 provides a useful tool to further investigate the regenerate epithelium.

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