The second messenger cyclic adenosine monophosphate (cAMP) plays an important role in cell proliferation, differentiation and apoptosis. In the present work, we evaluated the cAMP signaling in acute promyelocytic leukemia (APL) cells in the context of differentiation induced by all-trans retinoic acid (ATRA). There was a marked increase in the intracellular cAMP level within a few minutes after treatment with ATRA in APL cell line NB4 and fresh APL cells, whereas no such phenomenon was observed in NB4-R1 cells that are resistant to ATRAinduced maturation. In addition, the basal level of intracellular cAMP was lower in NB4-R1 than in NB4 cells. Mechanistic study showed that this induction of cAMP was mediated through the activation of adenylate cyclase. Moreover, we found that cAMPdependent protein kinase (PKA) activity was quickly upregulated in parallel in ATRA-treated NB4 cells, and the phosphorylation of RARa by PKA could increase its transactivation effect. Use of H-89, an inhibitor of PKA, could partially suppress the transcriptional expression of ATRA target genes and ATRAinduced differentiation of APL cells. Taken together, we suggested a crosstalk between ATRA-induced cytosolic pathway and nuclear pathway in APL cell differentiation.
Mammalians sex determination is well-known, and sophisticated mechanisms to sex control have been developed. However, effective sex control in poultry has not yet been developed. Through RNA-sequencing of the male gonads and ovarian tissues of chicken embryos up to 18.5 days, we identified the primary metabolic factors affecting male and female sex differentiation and gonadal development. Pkm2, an essential glycolysis-related protein, influences sex differentiation in chickens via Gapdh, a crucial hormone gene. Glycolysis-related sex regulation also involves epigenetic alterations such as transcription factor (Srf, Myb, Tead1), acetylation (Hdac3), and phosphorylation (Nfkbia, Ikbkb) modifications. Our findings support the concept that glycolysis and oxidative phosphorylation contribute upstream to sexual phenotypic development and maintenance.
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