Role of oculocerebrorenal syndrome of Lowe (OCRL) protein in megakaryocyte maturation, platelet production and functions: a study in patients with Lowe syndrome

2021 ◽  
Vol 192 (5) ◽  
pp. 909-921
Author(s):  
Marion Egot ◽  
Dominique Lasne ◽  
Sonia Poirault‐Chassac ◽  
Tristan Mirault ◽  
Dominique Pidard ◽  
...  
Keyword(s):  
Lowe Syndrome ◽  
Platelet Production ◽  
Oculocerebrorenal Syndrome

scholarly journals A Role of the Lowe Syndrome Protein OCRL in Early Steps of the Endocytic Pathway

2007 ◽  
Vol 13 (3) ◽  
pp. 377-390 ◽  
Author(s):  
Kai S. Erdmann ◽  
Yuxin Mao ◽  
Heather J. McCrea ◽  
Roberto Zoncu ◽  
Sangyoon Lee ◽  
...  
Keyword(s):  
Endocytic Pathway ◽  
Lowe Syndrome ◽  
Syndrome Protein

Low-dose decitabine promotes megakaryocyte maturation and platelet production in healthy controls and immune thrombocytopenia

2015 ◽  
Vol 113 (05) ◽  
pp. 1021-1034 ◽  
Author(s):  
Hai Zhou ◽  
Yu Hou ◽  
Xuena Liu ◽  
Jihua Qiu ◽  
Qi Feng ◽  
...  
Keyword(s):  
Immune Thrombocytopenia ◽  
Low Dose ◽  
Methylation Status ◽  
Healthy Controls ◽  
Trail Expression ◽  
Platelet Production ◽  
Potential Therapeutic Role ◽  
Platelet Release

SummaryImpaired megakaryocyte maturation and insufficient platelet production have been shown to participate in the pathogenesis of immune thrombocytopenia (ITP). Our previous study demonstrated that low expression of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) in megakaryocytes contributed to impaired platelet production in ITP. Decitabine (DAC), a demethylating agent, is known to promote cell differentiation and maturation at low doses. However, whether decitabine is potential in promoting megakaryocyte maturation and platelet release in ITP is unclear. In this study, we evaluated the effect of DAC on megakaryocyte maturation and platelet release in the presence of ITP plasma that has been shown to cause impaired megakaryocyte maturation and platelet production. We observed that low-dose DAC (10 nM) could significantly increase the number of mature polyploid (≥ 4N) megakaryocytes in cultures with plasma from healthy controls and more than one-half of ITP patients in vitro. Furthermore, the number of platelets released from these megakaryocytes significantly increased compared with those untreated with DAC. In these megakaryocytes, DAC significantly enhanced TRAIL expression via decreasing its promoter methylation status. These findings demonstrate that low-dose DAC can promote megakaryocyte maturation and platelet production and enhance TRAIL expression in megakaryocytes in healthy controls and ITP. The potential therapeutic role of low-dose DAC may be beneficial for thrombocytopenic disorders.H. Z. and Y. H. contributed equally to this work.

scholarly journals Lowe syndrome identified in the offspring of an oocyte donor who was an unknown carrier of a de novo mutation: a case report and review of the literature

2019 ◽  
Vol 13 (1) ◽  
Author(s):  
P. Tatsi ◽  
G. E. Papanikolaou ◽  
T. Chartomatsidou ◽  
I. Papoulidis ◽  
A. Athanasiadis ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Ethical Issues ◽  
De Novo ◽  
Dent Disease ◽  
De Novo Mutation ◽  
Lowe Syndrome ◽  
Genetic Constitution ◽  
Preimplantation Genetic Testing ◽  
Oculocerebrorenal Syndrome

Abstract Background Oculocerebrorenal syndrome of Lowe is an X-linked disorder with very low prevalence in the general population. The OCRL gene encodes the protein phosphatidylinositol 4,5-bisphosphate-5-phosphatase, a lipid phosphatase, located in the trans-Golgi network. Point mutations in the OCRL gene cause Lowe syndrome and Dent disease, which are characterized as a multisystemic disorder. The symptoms of Lowe syndrome are expressed primarily as dysfunction of the eyes, kidneys, and the central nervous system. Case presentation This report describes a case of a 31-year-old Georgian woman with a de novo pathogenic mutation causing oculocerebrorenal syndrome of Lowe, who was a volunteer in an oocyte donation program for in vitro fertilization purposes, and the outcome of the treatments of this particular donor’s oocyte receivers, describing the implications of the mutation for the children born as a result of the treatments. It raises important medical and ethical issues about the necessity of genetic testing of oocyte donors and the possibility of rare genetic disorders being inherited by the offspring of donors. Conclusion This particular case indicates the legal, medical, and emotional risks of utilizing donor oocytes from phenotypically healthy women, whose genetic constitution is unknown in terms of being silent carriers of rare diseases. In addition, all the necessary actions were followed; the further examinations that are required are mentioned. The donor and the offspring should be further tested. The remaining cryopreserved embryos should be destroyed or preimplantation genetic testing should be performed before they are utilized. Finally, all the people involved, the treated couples and the donor, alongside her family, should follow genetic and psychological counselling.

scholarly journals Mechanism of platelet production from megakaryocytes-role of proplatelet formation-

2006 ◽  
Vol 17 (3) ◽  
pp. 261-271 ◽  
Author(s):  
Hiroshi KOJIMA ◽  
Yukinori KOZUMA ◽  
Toshiro NAGASAWA
Keyword(s):  
Platelet Production ◽  
Proplatelet Formation

scholarly journals Regulation of Platelet Production and Life Span: Role of Bcl-xL and Potential Implications for Human Platelet Diseases

2020 ◽  
Vol 21 (20) ◽  
pp. 7591
Author(s):  
Emma C. Josefsson ◽  
William Vainchenker ◽  
Chloe James
Keyword(s):  
Life Span ◽  
Human Platelet ◽  
Inflammatory Diseases ◽  
Blood Platelets ◽  
Intrinsic Apoptosis ◽  
Tumour Angiogenesis ◽  
Platelet Production ◽  
Family Protein ◽  
Platelet Number

Blood platelets have important roles in haemostasis, where they quickly stop bleeding in response to vascular damage. They have also recognised functions in thrombosis, immunity, antimicrobal defense, cancer growth and metastasis, tumour angiogenesis, lymphangiogenesis, inflammatory diseases, wound healing, liver regeneration and neurodegeneration. Their brief life span in circulation is strictly controlled by intrinsic apoptosis, where the prosurvival Bcl-2 family protein, Bcl-xL, has a major role. Blood platelets are produced by large polyploid precursor cells, megakaryocytes, residing mainly in the bone marrow. Together with Mcl-1, Bcl-xL regulates megakaryocyte survival. This review describes megakaryocyte maturation and survival, platelet production, platelet life span and diseases of abnormal platelet number with a focus on the role of Bcl-xL during these processes.

MiR-223 is dispensable for platelet production and function in mice

2013 ◽  
Vol 110 (12) ◽  
pp. 1207-1214 ◽  
Author(s):  
Xavier Loyer ◽  
Simon Leierseder ◽  
Tobias Petzold ◽  
Lin Zhang ◽  
Steffen Massberg ◽  
...  
Keyword(s):  
Platelet Adhesion ◽  
Cell Types ◽  
Surface Expression ◽  
Wild Type ◽  
Platelet Production ◽  
Multiple Cell ◽  
And Function ◽  
Deficient Mice ◽  
Platelet Depletion

SummaryMicroRNAs (miRNAs) are key physiological regulators in multiple cell types. Here, we assessed platelet production and function in mice deficient in miR-223, one of the most abundantly expressed miRNAs in platelets and megakaryocytes. We found platelet number, size, lifespan as well as surface expression of platelet adhesion receptors to be unchanged in miR-223-deficient mice. Likewise, loss of miR-223 did not affect platelet activation, adhesion and aggregation and also had no effect on bleeding times. Moreover, miR-223 null megakaryocytes developed normally and were capable to form pro-platelets. However, we detected a transient delay in the recovery of platelet numbers following antibody-induced platelet depletion in miR-223-deficient animals. This delay was not observed after transplantation of bone marrow from miR-223-deficient animals into wild-type recipients, indicating a non-cell-autonomous role of miR-223 for thrombopoiesis. Overall, our data indicate a surprisingly modest role of miR-223 in platelet production, while the function of platelets does not seem to depend on miR-223.

SHPing in different directions in platelet production

Blood ◽  
2013 ◽  
Vol 121 (20) ◽  
pp. 4018-4019 ◽  
Author(s):  
Jorge Di Paola
Keyword(s):  
Platelet Function ◽  
Conditional Knockout ◽  
Murine Models ◽  
Platelet Production ◽  
Platelet Counts

In this issue of Blood, Mazharian and colleagues characterize Shp1 and Shp2 conditional knockout (KO) murine models, underscoring the role of these phosphatases not only on platelet function but also on megakaryocyte development and platelet counts and size.1

The role of class I, II and III PI 3-kinases in platelet production and activation and their implication in thrombosis

2016 ◽  
Vol 61 ◽  
pp. 33-41 ◽  
Author(s):  
Colin Valet ◽  
Sonia Severin ◽  
Gaëtan Chicanne ◽  
Pierre Alexandre Laurent ◽  
Frédérique Gaits-Iacovoni ◽  
...  
Keyword(s):  
Class I ◽  
Platelet Production
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