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PCSK9 regulates apoptosis in human neuroglioma u251 cells via mitochondrial signaling pathways.

ABSTRACT: Proprotein convertase subtilisin/kexin type 9 (PCSK9), belongs to a family of proprotein convertases (PCs), encodes a neural apoptosis-regulated convertase 1. However, the precise role of PCSK9 during glioma cells apoptosis has not been reported. Therefore, we examined the effects of knockdown and overexpression of PCSK9 on apoptosis of human neuroglioma U251 cells, and investigated the underlying mechanisms of apoptosis. We found that PCSK9 regulated cells proliferation as determined by CCK-8 and Hoechst staining analysis. In addition, western blot results showed that PCSK9 siRNA promote apoptosis via activation of caspase-3 and down-regulation of the anti-apoptotic proteins, XIAP and p-Akt, while PCSK9 overexpression inhibited apoptosis. Moreover, PCSK9 siRNA improved the ratio of Bax/Bcl-2 which leads to the release of cytochrome c, while PCSK9 overexpression decreased it. Taken together, these data demonstrate that PCSK9 may regulate apoptosis through mitochondrial pathway and is expected to be a promising therapeutic strategy for the malignant glioma.

SUBMITTER: Piao MX

PROVIDER: S-EPMC4440094 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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PCSK9 regulates apoptosis in human neuroglioma u251 cells via mitochondrial signaling pathways.

Piao Ming-Xue MX Bai Ji-Wei JW Zhang Peng-Fei PF Zhang Ya-Zhuo YZ

International journal of clinical and experimental pathology 20150301 3

Proprotein convertase subtilisin/kexin type 9 (PCSK9), belongs to a family of proprotein convertases (PCs), encodes a neural apoptosis-regulated convertase 1. However, the precise role of PCSK9 during glioma cells apoptosis has not been reported. Therefore, we examined the effects of knockdown and overexpression of PCSK9 on apoptosis of human neuroglioma U251 cells, and investigated the underlying mechanisms of apoptosis. We found that PCSK9 regulated cells proliferation as determined by CCK-8 a ...[more]

PMID: 26045785

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Project description:Acute inflammation (INF) and apoptosis are induced in monocytes by the generation of several factors, including the products of cytosolic oxygen free radicals (cROS) and the excessive influx of Ca2+ via the stimulation of TRPV1. These are main factors in the etiology of monocyte activation-induced inflammatory and neurodegenerative diseases. Importantly, the protective action of hydroxychloroquine (HCQ) treatment via the inhibition of TRPV1 on the levels of inflammatory factors, cROS, and apoptosis in acute INF (lipopolysaccharide, LPS)-exposed neuronal cells was recently reported. However, the relationships between acute INF via TRPV1 activation and HCQ in monocytes have not been fully clarified yet. The cell membrane of U937 human monocytes contains natural TRPV1. In the study plan, we used U937 cells in four main groups, namely control, HCQ (60 μM for 48 h), INF (1 μg/mL LPS for 16 h), and HCQ + INF. The current data indicate that LPS-induced acute INF caused the upregulation of excessive cytosolic Ca2+ accumulation via the stimulation of TRPV1 in the cells. The treatment of INF additionally upregulated the levels of apoptosis and cytokines (IL6, IL1β, and TNFα), due to upregulated cROS and lipid peroxidation levels as well as upregulated generation of caspase -3 (CAS3) and -9 (CAS9) but a decrease in glutathione and glutathione peroxidase. The expression levels of TRPV1, Bax, CAS3, and CAS9 were also upregulated by the treatment of LPS. However, treatment with HCQ and TRPV1 blocker (capsazepine) modulated the levels of cytokines, caspases, cROS, Ca2+ influx, and apoptosis through the modulation of TRPV1 in the U937 that were stimulated with LPS. In summary, the present data suggest TRPV1 activation through the acute INF (LPS)-induced inflammatory, oxidant, and apoptotic adverse actions in monocyte cells, whereas HCQ prevented adverse actions via the modulation of TRPV1. The results may be significant in the modulation of monocyte activation-caused inflammatory and neurodegenerative diseases.

Dataset Information

PCSK9 regulates apoptosis in human neuroglioma u251 cells via mitochondrial signaling pathways.

Publications

PCSK9 regulates apoptosis in human neuroglioma u251 cells via mitochondrial signaling pathways.

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