08 August 2018 : Laboratory Research
FSD-C10 Shows Therapeutic Effects in Suppressing oxidized low-density lipoprotein (ox-LDL)-Induced Human Brain Microvascular Endothelial Cells Apoptosis via Rho-Associated Coiled-Coil Kinase (ROCK)/Mitogen-Activated Protein Kinase (MAPK) SignalingXin Wang1ABCDEFG*, Rongyan Mao1ABDEF, Weiwei Chen1CDEF
Med Sci Monit 2018; 24: LBR5509-5516
BACKGROUND: ox-LDL-induced injury of brain microvascular endothelial cells (BMECs) is strongly associated with cerebral vascular diseases such as cerebral arterial atherosclerosis. ROCK inhibitor was proved to be anti-apoptotic and has been used in treating cerebral vascular diseases. Research on the neuroprotective effects of a novel ROCK inhibitor, FSD-C10, is still limited. The present study investigated the anti-apoptotic effect and underlying molecular mechanism of FSD-C10 in ox-LDL-mediated apoptosis of BMECs.
MATERIAL AND METHODS: ox-LDL and/or FSD-C10 were used to incubate immortalized human BMECs. MTT assay was used to assess cell viability. Cell apoptosis was evaluated by TUNEL assay. A colorimetric method was used to assess ROCK activity. Western blot analysis was used to examine the expression and phosphorylation levels of proteins.
RESULTS: ox-LDL incubation reduced the viability of BMECs by inducing cell apoptosis in a concentration-dependent manner. ROCK activity was also elevated by ox-LDL incubation in BMECs in a concentration-dependent manner. Expression level of Bcl2 was reduced while expression levels of Bax and active caspase3 were increased by ox-LDL treatment in a concentration-dependent manner. ox-LDL also increased the phosphorylation levels of p38, JNK, and ERK1/2 in a concentration-dependent manner. FSD-C10 treatment increased the cell viability by reducing apoptosis of BMECs exposed to ox-LDL. Moreover, FSD-C10 was found to suppress the phosphorylation levels of p38, JNK, and ERK1/2 and the expression levels of Bax and active caspase3 in ox-LDL treated BMECs.
CONCLUSIONS: FSD-C10 increases cell viability in ox-LDL-treated BMECs by reducing cell apoptosis. ROCK/MAPKs-mediated apoptosis appears to be the underlying molecular mechanism.
Keywords: Receptors, Oxidized LDL, rho-Associated Kinases
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