Nuclear Inositide Signaling Via Phospholipase C.

The existence of an independent nuclear inositide pathway distinct from the cytoplasmic one has been demonstrated in different physiological systems and in diseases. In this prospect we analyze the role of PI-PLCß1 nuclear isoform in relation to the cell cycle regulation, the cell differentiation, and different physiopathological pathways focusing on the importance of the nuclear localization from both molecular and clinical point of view. PI-PLCß1 is essential for G1/S transition through DAG and Cyclin D3 and plays also a central role in G2/M progression through Cyclin B1 and PKCα. In the differentiation process of C2C12 cells PI-PLCß1 increases in both myogenic differentiation and osteogenic differentiation. PI-PLCß1 and Cyclin D3 reduction has been observed in Myotonic Dystrophy (DM) suggesting a pivotal role of these enzymes in DM physiopathology. PI-PLCß1 is also involved in adipogenesis through a double phase mechanism. Moreover, PI-PLCß1 plays a key role in the normal hematopoietic differentiation where it seems to decrease in erythroid differentiation and increase in myeloid differentiation. In Myelodysplastic Syndromes (MDS) PI-PLCß1 has a genetic and epigenetic relevance and it is related to MDS patients' risk of Acute Myeloid Leukemia (AML) evolution. In MDS patients PI-PLCß1 seems to be also a therapeutic predictive outcome marker. In the central nervous system, PI-PLCß1 seems to be involved in different pathways in both brain cortex development and synaptic plasticity related to different diseases. Another PI-PLC isozyme that could be related to nuclear activities is PI-PLCζ that is involved in infertility processes. J. Cell. Biochem. 118: 1969-1978, 2017. © 2017 Wiley Periodicals, Inc.

An increased expression of PI-PLCß1 is associated with myeloid differentiation and a longer response to azacitidine in myelodysplastic syndromes.

This study tested the hypothesis that PI-PLCß1 is associated with myeloid differentiation and that its expression could be useful for predicting the response of MDS patients to azacitidine, as the clinical effect of epigenetic treatments is often detectable only after several cycles of therapy. To this end, PI-PLCß1 was quantified on 70 MDS patients (IPSS risk: 13 Low, 20 Int-1, 31 Int-2, 6 High) at baseline and during the first 3 cycles of azacitidine. Results were then compared with the hematologic response, as assessed after the sixth cycle of azacitidine therapy. Overall, 60 patients completed 6 cycles of azacitidine, and for them, a clinical and molecular evaluation was possible: 37 of these patients (62%) showed a specific increase of PI-PLCß1 mRNA within the first 3 cycles, which was associated with a longer duration of response and with an increased myeloid differentiation, as evidenced by PI-PLCγ2 induction and the recruitment of specific myeloid-associated transcription factors to the PI-PLCß1 promoter during azacitidine response. Moreover, the increase of cyclin D3 gene expression throughout all of the therapy showed that PI-PLCß1-dependent signaling is indeed activated in azacitidine responder patients. Taken together, our results show that PI-PLCß1 quantification in MDS predicts the response to azacitidine and is associated with an increased myeloid differentiation.

Hepato-gastric and spleno-mesenteric arterial trunks: anatomical variation report and review of literature.

The celiac trunk is one of the main arteries arising from abdominal aorta and supplies blood to several abdominal organs. The typical branching in left gastric, splenic and common hepatic arteries undergoes relatively frequent variations. The authors report a rare variation of the celiac trunk in a Caucasian cadaver, with a hepato-gastric and a spleno-mesenteric arterial trunks which arise from the abdominal aorta in a routine dissection of a 98-year-old male cadaver. Detailed knowledge of this kind of variations is important to plan and perform surgery in this district.