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Short-chain chlorinated paraffins may induce thymic aging in mice by activating PERK-CHOP.
Bai, Mingxin; Lei, Jiawei; Li, Fan; Wang, Xuning; Fu, Hu; Yan, Zhengli; Huang, Xin; Zhu, Yongfei.
Afiliación
  • Bai M; Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Preventive Medicine, Medical School, Hunan Normal University, Changsha, 410013, Hunan, China.
  • Lei J; Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Preventive Medicine, Medical School, Hunan Normal University, Changsha, 410013, Hunan, China.
  • Li F; Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Preventive Medicine, Medical School, Hunan Normal University, Changsha, 410013, Hunan, China.
  • Wang X; Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Preventive Medicine, Medical School, Hunan Normal University, Changsha, 410013, Hunan, China.
  • Fu H; Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Preventive Medicine, Medical School, Hunan Normal University, Changsha, 410013, Hunan, China; Key Laboratory of Protein Chemistry and Fish Developmental Biology of Ministry of Education, Hunan Normal U
  • Yan Z; Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Preventive Medicine, Medical School, Hunan Normal University, Changsha, 410013, Hunan, China; Key Laboratory of Protein Chemistry and Fish Developmental Biology of Ministry of Education, Hunan Normal U
  • Huang X; Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Preventive Medicine, Medical School, Hunan Normal University, Changsha, 410013, Hunan, China. Electronic address: xin.huang@hunnu.edu.cn.
  • Zhu Y; Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Preventive Medicine, Medical School, Hunan Normal University, Changsha, 410013, Hunan, China; Key Laboratory of Protein Chemistry and Fish Developmental Biology of Ministry of Education, Hunan Normal U
Environ Pollut ; 357: 124438, 2024 Sep 15.
Article en En | MEDLINE | ID: mdl-38942270
ABSTRACT
Humans indirectly consume approximately 0.02 mg/kg/day of short-chained chlorinated paraffins (SCCPs) through the environment; however, the thymic senescence/damage induced by SCCPs has not been assessed. In this study, 16 female mice (4-week-old) per group were orally administered 0, 0.01, 0.1, and 1 mg/kg/day of SCCPs for 21 days, and the phenotypes and levels of superoxide dismutase (SOD), malondialdehyde (MDA), Tß4, αß TCR, SA-ß-Gal, GRP78, PERK/CHOP, P53/P21, and CASPASE-1 of the thymus were assessed as indicators. Another group comprising 16 mice was killed at 4-week-old and these indicators were assessed. Thereafter, the thymuses cultured in vitro were exposed to 0, 14, 140, and 1400 µg/L SCCPs, respectively, and the above indicators were measured after 7-day. Based on the results, the oral administration of ≥0.01 mg/kg/day SCCPs to mice and ≥14 µg/L of SCCPs in medium caused thymic aging features, such as a decrease in the ratio of cortex to medulla, gradual blurring of the boundary between the cortex and medulla, dose-dependent oxidative stress (decreased SOD and increased MDA), and decreased levels of Tß4 and αß TCRs in the thymus. The oral administration of ≥1 mg/kg/day of SCCPs also impeded the growth and development of female mice and their thymuses. Exposure to the low levels of SCCPs activated PERK-CHOP in the mouse thymus, which modulated increases in SA-ß-Gal, IL-1ß, P53, and CASPASE-1 in vivo and in vitro. Overall, environmental levels and human blood concentrations (14.8-1400 µg/L) of SCCPs may induce mouse thymus senescence by activating PERK-CHOP in vivo and in vitro, respectively.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Timo / Factor de Transcripción CHOP / Chaperón BiP del Retículo Endoplásmico Límite: Animals Idioma: En Revista: Environ Pollut Asunto de la revista: SAUDE AMBIENTAL Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Timo / Factor de Transcripción CHOP / Chaperón BiP del Retículo Endoplásmico Límite: Animals Idioma: En Revista: Environ Pollut Asunto de la revista: SAUDE AMBIENTAL Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido