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  3. Exposure to short-chain chlorinated paraffins induces astrocyte activation via JAK2/STAT3 signaling pathway

Exposure to short-chain chlorinated paraffins induces astrocyte activation via JAK2/STAT3 signaling pathway

  • Ecotoxicol Environ Saf. 2022 Nov 11;248:114268. doi: 10.1016/j.ecoenv.2022.114268.
Wenjie Ding 1,  Zixuan Zhao 1,  Yudan Zheng 1,  Rui Wang 1,  Zeyao Zhang 1,  Ziyang Zhang 1,  Xiangdong Wang 1,  Shali Yu 1,  Lei Liu 2,  Rongrong Huang 3,  Xinyuan Zhao 4,  Qiyun Wu 5
Affiliations

Affiliations

  • 1 Department of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong University, Nantong 226019, China.
  • 2 Department of Pathology, Affiliated Hospital of Nantong University, Nantong 226006, China.
  • 3 Department of Pharmacy, Affiliated Hospital of Nantong University, Nantong 226006, China.
  • 4 Department of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong University, Nantong 226019, China. Electronic address: [email protected].
  • 5 Department of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong University, Nantong 226019, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China. Electronic address: [email protected].
PMID: 36375367 DOI: 10.1016/j.ecoenv.2022.114268
Abstract

In the last few decades, short-chain chlorinated paraffins (SCCPs) have become the most heavily produced monomeric organohalogen compounds, and have been reported to induce multiple organ toxicity. However, the effects of SCCPs on the central nervous system are unknown. In the present study, we show that SCCP exposure induced astrocyte proliferation and increased the expression of two critical markers of astrocyte activation, glial fibrillary acidic protein and inducible nitric oxide synthase, in vivo and in vitro. SCCP exposure also increased inflammatory factory gene expression. Moreover, SCCP treatment triggered Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signalling, as shown by increased phosphorylation and STAT3 translocation to the nucleus. Both JAK2 and STAT3 inhibition effectively attenuated SCCP-induced astrocyte activation. Finally, JAK2 inhibition significantly rescued STAT3 phosphorylation and nuclear translocation. Taken together, JAK2/STAT3 pathway activation contributed to SCCP-induced astrocyte activation. These data will help elucidate the molecular mechanism underlying SCCP-induced neurotoxicity.

Keywords

Astrocyte activation; JAK2/STAT3 signal pathway; Neurotoxicity; Short-chain chlorinated paraffins.

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