Nitric oxide, an endogenous regulator of Dictyostelium discoideum differentiation.
We have previously demonstrated that nitric oxide (NO)-generating compounds inhibit D. discoideum differentiation by preventing the initiation of cAMP pulses (Tao, Y., Howlett, A. and Klein, C. (1996) Cell. Signal. 8, 37-43). In the present study, we demonstrate that cells produce NO at a relatively constant rate during the initial phase of their developmental cycle. The addition of oxyhemoglobin, an NO scavenger, stimulates cell aggregation, suggesting that NO has a negative effect on the development of aggregation competence. Starvation of cells in the presence of glucose, which has been shown to prevent the initiation of cAMP pulses (Darmon, M. and Klein, C. (1978) Dev. Biol. 63, 377-389), results in an increased production of NO. The inhibition of cell aggregation by glucose treatment can be reversed by oxyhemoglobin. These findings indicate that NO is a signaling molecule for D. discoideum cells and that physiological or environmental conditions that enhance external NO levels will delay the initiation of cAMP pulses, which are essential for cell differentiation.
Tao
Y P
YP
Department of Biochemistry and Molecular Biology, St. Louis University School of Medicine, MO 63104, USA.
Misko
T P
TP
Howlett
A C
AC
Klein
C
C
D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics; D002449:Cell Aggregation / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D003470:Culture Media; D000242:Cyclic AMP / Q000378:metabolism; D004023:Dictyostelium / Q000166:cytology* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D015870:Gene Expression; D005947:Glucose / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D010108:Oxyhemoglobins / Q000494:pharmacology; D015800:Protozoan Proteins; D015398:Signal Transduction
D015815:Cell Adhesion Molecules; D003470:Culture Media; D010108:Oxyhemoglobins; D015800:Protozoan Proteins; C052291:cell cohesion molecule, Dictyostelium; D009569:Nitric Oxide; D000242:Cyclic AMP; D005947:Glucose