Protective effect of CTRP6 on cerebral ischemia/reperfusion injury by attenuating inflammation, oxidative stress and apoptosis in PC12 cells

Li,Ying; Sun,Jie; Gu,Lei; Gao,Xufang

doi:10.3892/mmr.2020.11108

Protective effect of CTRP6 on cerebral ischemia/reperfusion injury by attenuating inflammation, oxidative stress and apoptosis in PC12 cells

Authors:
- Ying Li
- Jie Sun
- Lei Gu
- Xufang Gao
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Affiliations: Rehabilitation Centre, Beijing Xiaotangshan Hospital, Beijing 102211, P.R. China, Department of Neurology, General Hospital of The Yangtze River Shipping and Wuhan Brain Hospital, Wuhan, Hubei 430010, P.R. China
Published online on: May 4, 2020 https://doi.org/10.3892/mmr.2020.11108
Pages: 344-352
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The newly identified C1q/tumor necrosis factor (TNF)-related protein-6 (CTRP6) is a highly conserved paralog of adiponectin with modulatory effects on metabolism and inflammation. However, the role of CTRP6 in cerebral ischemia/reperfusion (I/R) injury remains unknown. The aim of the present study was to explore the protective effects of CTRP6 against cerebral I/R injury and elucidate the possible underlying mechanisms. Oxygen‑glucose deprivation and reperfusion (OGD/R) was used to induce an I/R injury model in vitro. Western blotting, reverse transcription‑quantitative PCR, ELISA and flow cytometry analysis were used to measure the levels of CTRP6 along with those of inflammation‑, oxidative stress‑ and apoptosis‑related cytokines. The results indicated that CTRP6 expression was markedly downregulated following OGD/R. OGD/R also increased i) the activities of pro‑inflammatory factors TNF‑α, interleukin (IL)‑1β, IL‑6 and the levels of the oxidative products reactive oxygen species and malondialdehyde; ii) the ratio of apoptotic PC12 cells and iii) the expression of the pro‑apoptotic proteins Bax, cleaved caspase‑3 and cleaved caspase‑9. In addition, the activities of the anti‑inflammatory factors IL‑10 and superoxide dismutase and the expression of the anti‑apoptotic protein Bcl‑2 were decreased. However, overexpression of CTRP6 rescued OGD/R‑stimulated exacerbation of inflammation, oxidative stress and apoptosis. Mechanistically, OGD/R activated Ras homolog family member A (RhoA)/Rho‑associated coiled‑coil‑containing protein kinase (Rock)/phosphatase and tensin homologue deleted on chromosome 10 (PTEN) signaling, whereas CTRP6 overexpression restored the expression of RhoA, Rock, PTEN, phosphoinositide 3‑kinase (PI3K) and protein kinase B (Akt). Furthermore, when CTRP6 and RhoA were overexpressed at the same time, RhoA abolished the protective effects of CTRP6 overexpression on OGD/R‑induced inflammation, oxidative stress and apoptosis, while the presence of a PTEN inhibitor recovered the protective effects of CTRP6. Taken together, the findings of the present study indicate that CTRP6 attenuates cerebral ischemia/reperfusion‑induced inflammation, oxidative stress and apoptosis via inhibiting the RhoA/Rock/PTEN pathway, thereby activating PI3K/Akt signaling.

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