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Protective effects of fusidic acid against sodium nitroprusside-induced apoptosis in C6 glial cells

Park, Euteuma; Kim, Do Kyungb; Kim, Chun-Sungc; Kim, Jae-Sungd; Kim, Seunge; Chun, Hong Sunga

doi: 10.1097/WNR.0000000000001354
Cellular, Molecular and Developmental Neuroscience
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Fusidic acid, a steroidal antibiotic, possesses antimicrobial, antioxidant, and anti-inflammatory properties, but the effect of fusidic acid against neurodegenerative disease-related cell death has not been studied. Here, we investigated the protective effects of fusidic acid on sodium nitroprusside (SNP)-induced toxicity in C6 glial cells. Fusidic acid (5–20 μM) prevented SNP (100 μM)-induced cell death dose dependently, and effectively attenuated SNP-induced generation of nitric oxide (NO), total reactive oxygen species (ROS), and peroxynitrite (ONOO). Fusidic acid (20 μM) pretreatment significantly suppressed SNP (100 μM)-induced apoptotic events, such as nuclear condensation and caspase-3 activation. In addition, fusidic acid effectively attenuated SNP-induced endoplasmic reticulum (ER) stress markers, such as GRP78, IRE1, ATF6, PERK, XBP1s, eIF2α, CHOP, and caspase-12. A specific adenosine monophosphate-activated protein kinase (AMPK) inhibitor, compound C (10 μM), reversed the preventive effects of fusidic acid against SNP-induced cytotoxicity, CHOP elevation, and caspase-3 activation. These results suggest that fusidic acid can protect C6 glial cells against cytotoxicity, through the regulation of AMPK pathway and apoptotic events.

Departments of aBiomedical Science

bOral Physiology

cOral Biochemistry

dInstitute of Dental Science, School of Dentistry, Chosun University

eDepartment of Food Science and Biotechnology, Gwangju University, Gwangju, Republic of Korea

Received 7 September 2019 Accepted 13 September 2019

Correspondence to Dr. Hong Sung Chun, PhD, Department of Biomedical Science, Chosun University, 309 Pilmun-daero, Gwangju 61452, Republic of Korea, Tel/fax: +82 62 230 6609; e-mail: hsjeon@chosun.ac.kr

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