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The Mechanism of Mitochondria-Mediated Pathway in the Apoptosis of Platelets in Immune-Induced Bone Marrow Failure.
- Source :
-
The Chinese journal of physiology [Chin J Physiol] 2017 Dec 31; Vol. 60 (6), pp. 338-344. - Publication Year :
- 2017
-
Abstract
- Excessive platelet apoptosis is one of the pathogenic causes of immune-induced bone marrow failure (BMF). The aim of the present study was to explore the role of mitochondria-mediated pathway in the apoptosis of platelets in immune-induced BMF. An immune-induced BMF model was established in mice, which were randomly divided into three groups: normal control (CTL) group, BMF group and cyclosporine (CSA) group (n = 10 in each group). Mice were given 0.027 g/kg CSA daily in the CSA group. Platelet count (PLT), mitochondrial transmembrane potential (ΔΨm), cytochrome C (CytC), phosphatidylserine (PS), calcium ion (Ca²⁺) and expression of proteins of the mitochondrial apoptotic pathway, including Bak, Bax, caspase-3, caspase-8 and caspase-9, was examined and compared. Compared with the CTL group, the BMF group had significantly a lower level of PLC and ΔΨm, but higher levels of CytC, PS, Ca²⁺ and higher expression levels of Bak, Bax, cleaved caspase-9 and cleaved caspase-3 (P < 0.05). CSA restored the above changes in the BMF model (P < 0.05). Further studies showed that intravenous injection of the caspase-9 inhibitor Z-LE(OMe)HD(OMe)-fluoromethylketone (FMK) into the mice could significantly inhibit apoptosis of the platelets and the effect of CSA treatment when compared to the BMF group, and exerted a better protective effect from apoptosis if the caspase-9 inhibitor was combined with the CSA treatment. These results revealed that platelet apoptosis may play an important role in the reduction of platelet of immune-induced BMF probably through the mitochondrial pathway.<br />Competing Interests: The authors declare that they have no conflict of interests related to this work.
- Subjects :
- Animals
Bone Marrow Failure Disorders
Female
Male
Mice
Mice, Inbred C57BL
Anemia, Aplastic pathology
Anemia, Aplastic physiopathology
Apoptosis physiology
Blood Platelets pathology
Bone Marrow Diseases pathology
Bone Marrow Diseases physiopathology
Hemoglobinuria, Paroxysmal pathology
Hemoglobinuria, Paroxysmal physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 0304-4920
- Volume :
- 60
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Chinese journal of physiology
- Publication Type :
- Academic Journal
- Accession number :
- 29241307
- Full Text :
- https://doi.org/10.4077/CJP.2017.BAF484