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) Signaling
Xin Wang1ABCDEFG*, Rongyan Mao1ABDEF, Weiwei Chen1CDEFDOI: 10.12659/MSM.911481
Med Sci Monit 2018; 24: LBR5509-5516
Abstract
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
Editorial
01 July 2022 : Editorial
Editorial: World Health Organization (WHO) Variants of Concern Lineages Under Monitoring (VOC-LUM) in Response to the Global Spread of Lineages and Sublineages of Omicron, or B.1.1.529, SARS-CoV-2DOI: 10.12659/MSM.937676
Med Sci Monit 2022; 28:e937676
SARS-CoV-2/COVID-19
27 June 2022 : Clinical Research
Shoulder Injury Related to Vaccine Administration (SIRVA) in 16 Patients Following COVID-19 Vaccination Who...Med Sci Monit In Press; DOI: 10.12659/MSM.937430
04 June 2022 : Clinical Research
Screening for SARS-CoV-2 Infection in Students at the Medical University of Warsaw, Poland Between November...Med Sci Monit 2022; 28:e936962
30 May 2022 : Clinical Research
Effects of Wearing Face Masks on Exercise Capacity and Ventilatory Anaerobic Threshold in Healthy Subjects ...Med Sci Monit 2022; 28:e936069
27 May 2022 : Clinical Research
Factors Associated with Falls During Hospitalization for Coronavirus Disease 2019 (COVID-19)Med Sci Monit 2022; 28:e936547
In Press
05 Jul 2022 : Clinical Research
Attention-Deficit/Hyperactivity Disorder (ADHD) and Time Perception in Adults: Do Adults with Different ADH...Med Sci Monit In Press; DOI: 10.12659/MSM.936849
01 Jul 2022 : Clinical Research
Does Early-Period Patient Dissatisfaction Turn Into Satisfaction Over Time After Total Knee Replacement?Med Sci Monit In Press; DOI: 10.12659/MSM.936792
30 Jun 2022 : Laboratory Research
Bcl-2 19-kDa Interacting Protein 3 (BNIP3)-Mediated Mitophagy Attenuates Intermittent Hypoxia-Induced Human...Med Sci Monit In Press; DOI: 10.12659/MSM.936760
30 Jun 2022 : Clinical Research
Antioxidant System and Ions Concentrations After Femoral Neck and Resurfacing Hip ArthroplastyMed Sci Monit In Press; DOI: 10.12659/MSM.936335
Most Viewed Current Articles
30 Dec 2021 : Clinical Research
Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...DOI :10.12659/MSM.935379
Med Sci Monit 2021; 27:e935379
08 Mar 2022 : Review article
A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...DOI :10.12659/MSM.936292
Med Sci Monit 2022; 28:e936292
13 Nov 2021 : Clinical Research
Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...DOI :10.12659/MSM.932788
Med Sci Monit 2021; 27:e932788
01 Nov 2020 : Review article
Long-Term Respiratory and Neurological Sequelae of COVID-19DOI :10.12659/MSM.928996
Med Sci Monit 2020; 26:e928996