title: Repeated exposure to far infrared ray attenuates acute restraint stress in mice via inhibition of JAK2/STAT3 signaling pathway by induction of glutathione peroxidase-1.
abstract: Exposure to far-infrared ray (FIR) has been shown to exert beneficial effects on cardiovascular and emotional disorders. However, the precise underlying mechanism mediated by FIR remains undetermined. Since restraint stress induces cardiovascular and emotional disorders, the present study investigated whether exposure to FIR affects acute restraint stress (ARS) in mice. c-Fos-immunoreactivity (IR) was significantly increased in the paraventricular hypothalamic nucleus (PVN) and dorsomedial hypothalamic nucleus (DMH) in response to ARS. The increase in c-Fos-IR parallels that in oxidative burdens in the hypothalamus against ARS. Exposure to FIR significantly attenuated increases in the c-Fos-IR, oxidative burdens and corticosterone level. ARS elicited decreases in GSH/GSSG ratio, cytosolic Cu/Zn-superoxide dismutase (SOD-1), glutathione peroxidase (GPx), and glutathione reductase (GR) activities. FIR-mediated attenuation was particularly observed in ARS-induced decrease in GPx, but not in SOD-1 or GR activity. Consistently, ARS-induced decreases in GPx-1-immunoreactivity in PVN and DMH, and decreases in GPx-1 expression in the hypothalamus were significantly attenuated by FIR. ARS-induced significant increases in phosphorylation of JAK2/STAT3, and nuclear translocation and DNA-binding activity of NFκB were observed in the hypothalamus. Exposure to FIR selectively attenuated phosphorylation of JAK2/STAT3, but did not diminish nuclear translocation and DNA-binding activity of NFκB, suggesting that JAK2/STAT3 constitutes a critical target for FIR-mediated pharmacological potential. ARS-induced increase in c-Fos-IR in the PVN and DMH of non-transgenic mice was significantly attenuated by FIR exposure or JAK2/STAT3 inhibitor AG490. GPx-1 overexpressing transgenic mice significantly protected increases in the c-Fos-IR and corticosterone level induced by ARS. However, neither FIR exposure nor AG490 significantly affected attenuations by genetic overexpression of GPx-1. Moreover, AG490 did not exhibit any additional positive effects against the attenuation by genetic overexpression of GPx-1 or FIR exposure. Our results indicate that exposure to FIR significantly protects ARS-induced increases in c-Fos-IR and oxidative burdens via inhibition of JAK2/STAT3 signaling by induction of GPx-1.
authors: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea.
authors: Thai-Ha Nguyen
authors: TH
authors: Tran
authors: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea.
authors: Huynh Nhu
authors: HN
authors: Mai
authors: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea. Electronic address: shinej@kangwon.ac.kr.
authors: Eun-Joo
authors: EJ
authors: Shin
authors: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea.
authors: Yunsung
authors: Y
authors: Nam
authors: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea.
authors: Bao Trong
authors: BT
authors: Nguyen
authors: Clinical Pharmacy, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea.
authors: Yu Jeung
authors: YJ
authors: Lee
authors: Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea.
authors: Ji Hoon
authors: JH
authors: Jeong
authors: Physical Chemistry Department, University of Medicine and Pharmacy, Ho Chi Minh City 760000, Viet Nam.
authors: Hoang-Yen Phi
authors: HY
authors: Tran
authors: Department of Internal Medicine, Medical School, Kangwon National University, Chunchon 200-701, Republic of Korea.
authors: Eun-Hee
authors: EH
authors: Cho
authors: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, KonKuk University, Seoul 143-701, Republic of Korea.
authors: Seung-Yeol
authors: SY
authors: Nah
authors: Department of Animal Science, Cornell University, Ithaca, New York 14853, USA.
authors: Xin Gen
authors: XG
authors: Lei
authors: Department of Regional Pharmaceutical Care and Sciences, Graduate School of Pharmaceutical Sciences, Meijo University, Nagoya, Japan; NPO, Japanese Drug Organization of Appropriate Use and Research, Nagoya 468-8503, Japan.
authors: Toshitaka
authors: T
authors: Nabeshima
authors: College of Forest and Environmental Sciences, Kangwon National University, Chunchon 200-701, Republic of Korea.
authors: Nam Hun
authors: NH
authors: Kim
authors: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, Republic of Korea. Electronic address: kimhc@kangwon.ac.kr.
authors: Hyoung-Chun
authors: HC
authors: Kim
mesh_terms: D000818:Animals; D004302:Dorsomedial Hypothalamic Nucleus / Q000378:metabolism / Q000528:radiation effects; D004790:Enzyme Induction; D005979:Glutathione Peroxidase / Q000096:biosynthesis* / Q000528:radiation effects; D007259:Infrared Rays / Q000627:therapeutic use*; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012149:Restraint, Physical / Q000523:psychology*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000528:radiation effects; D015398:Signal Transduction / Q000502:physiology / Q000528:radiation effects; D013315:Stress, Psychological / Q000378:metabolism* / Q000517:prevention & control; D000094765:Glutathione Peroxidase GPX1
chemical_list: D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D005979:Glutathione Peroxidase; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse
keywords: Acute restraint stress; Corticosterone; FIR; GPx-1 overexpressing transgenic mice; Hypothalamus; JAK2/STAT3