Impact of Methyl-ß-Cyclodextrin and Apolipoprotein A-I on The Expression of ATP-Binding Cassette Transporter A1 and Cholesterol Depletion in C57BL/6 Mice Astrocytes.

OBJECTIVE: Dysregulation of cholesterol metabolism in the brain is responsible for many lipid storage disorders, including Niemann-Pick disease type C (NPC). Here, we have investigated whether cyclodextrin (CD) and apolipoprotein A-I (apoA-I) induce the same signal to inhibit cell cholesterol accumulation by focusing on the main proteins involved in cholesterol homeostasis in response to CD and apoA-I treatment. MATERIALS AND METHODS: In this experimental study, astrocytes were treated with apoA-I or CD and then lysed in RIPA buffer. We used Western blot to detect protein levels of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR) and ATP-binding cassette transporter A1 (ABCA1). Cell cholesterol content and cholesterol release in the medium were also measured. RESULTS: ApoA-I induced a significant increase in ABCA1 and a mild increase in HMGCR protein level, whereas CD caused a significant increase in HMGCR with a significant decrease in ABCA1. Both apoA-I and CD increased cholesterol release in the medium. A mild, but not significant increase, in cell cholesterol content was seen by apoA-I; however, a significant increase in cell cholesterol was detected when the astrocytes were treated with CD. CONCLUSION: CD, like apoA-I, depletes cellular cholesterol. This depletion occurs in a different way from apoA-I that is through cholesterol efflux. Depletion of cell cholesterol with CDs led to reduced protein levels of ABCA1 along with increased HMGCR and accumulation of cell cholesterol. This suggested that CDs, unlike apoA-I, could impair the balance between cholesterol synthesis and release, and interfere with cellular function that depends on ABCA1.

The role and clinical implications of the endosteal niche and osteoblasts in regulating leukemia

Osteoblasts are one among the critical components of the endosteal bone marrow (BM) niche. In addition to hematopoietic stem cell fate, their role in leukemogenesis as well as metastasis of a variety of cancers has been demonstrated in various studies. In this regard, endosteal niche can have a dual role as an initiator and protective role against leukemia. Knowledge of growth factors, chemokines and cytokines secreted by osteoblasts as well as their interaction with signaling pathways inform our understanding of the development, prognosis, recurrence and treatment of malignant BM diseases. Clinical progress in targeting the endosteal niche is also discussed (AU)

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The role and clinical implications of the endosteal niche and osteoblasts in regulating leukemia.

Osteoblasts are one among the critical components of the endosteal bone marrow (BM) niche. In addition to hematopoietic stem cell fate, their role in leukemogenesis as well as metastasis of a variety of cancers has been demonstrated in various studies. In this regard, endosteal niche can have a dual role as an initiator and protective role against leukemia. Knowledge of growth factors, chemokines and cytokines secreted by osteoblasts as well as their interaction with signaling pathways inform our understanding of the development, prognosis, recurrence and treatment of malignant BM diseases. Clinical progress in targeting the endosteal niche is also discussed.