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Phospholipase C delta 4 (PLCδ4) is a nuclear protein involved in cell proliferation and senescence in mesenchymal stromal stem cells
Cellular Signalling ( IF 4.4 ) Pub Date : 2018-06-01 , DOI: 10.1016/j.cellsig.2018.05.011
Marianna Kunrath-Lima , Marcelo Coutinho de Miranda , Andrea da Fonseca Ferreira , Camila Cristina Fraga Faraco , Mariane Izabella Abreu de Melo , Alfredo Miranda Goes , Michele Angela Rodrigues , Jerusa Araújo Quintão Arantes Faria , Dawidson Assis Gomes

Ca2+ is an important second messenger, and it is involved in many cellular processes such as cell death and proliferation. The rise in intracellular Ca2+ levels can be due to the generation of inositol 1,4,5-trisphosphate (InsP3), which is a product of phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis by phospholipases C (PLCs), that leads to Ca2+ release from endoplasmic reticulum by InsP3 receptors (InsP3R). Ca2+ signaling patterns can vary in different regions of the cell and increases in nuclear Ca2+ levels have specific biological effects that differ from those of Ca2+ increase in the cytoplasm. There are PLCs in the cytoplasm and nucleus, but little is known about the functions of nuclear PLCs. This work aimed to characterize phenotypically the human PLCδ4 (hPLCδ4) in mesenchymal stem cells. This nuclear isoform of PLC is present in different cell types and has a possible role in proliferative processes. In this work, hPLCδ4 was found to be mainly nuclear in human adipose-derived mesenchymal stem cells (hASC). PLCδ4 knockdown demonstrated that it is essential for hASC proliferation, without inducing cell death. An increase of cells in G1, and a reduction of cells on interphase and G2/M in knockdown cells were seen. Furthermore, PLCδ4 knockdown increased the percentage of senescent cells, p16INK4A+ and p21Cip1 mRNAs expression, which could explain the impaired cell proliferation. The results show that hPLCδ4 is in involved in cellular proliferation and senescence in hASC.



中文翻译:

磷脂酶C delta 4(PLCδ4)是一种核蛋白,参与间充质基质干细胞的细胞增殖和衰老

Ca 2+是重要的第二信使,它参与许多细胞过程,例如细胞死亡和增殖。细胞内Ca 2+水平的升高可能是由于肌醇1,4,5-三磷酸(InsP 3)的产生,它是磷脂酶C(PLCs)水解磷脂酰肌醇4,5-双磷酸(PIP 2)的产物。 ,导致InsP 3受体(InsP 3 R)从内质网释放Ca 2+。的Ca 2+的信令模式可以在小区的不同区域并在核的Ca的增加而变化2+从那些的Ca不同级别具有特定生物学效应2+细胞质增加。在细胞质和细胞核中都有PLC,但是对核PLC的功能知之甚少。这项工作旨在表型表征间充质干细胞中的人PLCδ4(hPLCδ4)。PLC的这种核同工型存在于不同的细胞类型中,并可能在增殖过程中发挥作用。在这项工作中,hPLCδ4被发现主要是人类脂肪来源的间充质干细胞(hASC)中的核。PLCδ4敲低表明它对hASC增殖至关重要,而不会诱导细胞死亡。观察到G1细胞增加,而敲低细胞中相间和G2 / M细胞减少。此外,PLCδ4敲低增加了衰老细胞,p16 INK4A +p21 Cip1的百分比mRNA的表达,可以解释细胞增殖受损。结果表明,hPLCδ4参与了hASC中的细胞增殖和衰老。

更新日期:2018-06-01
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