2. Academic Validation
  3. Cadmium induced cerebral toxicity via modulating MTF1-MTs regulatory axis

Cadmium induced cerebral toxicity via modulating MTF1-MTs regulatory axis

  • Environ Pollut. 2021 Sep 15:285:117083. doi: 10.1016/j.envpol.2021.117083.
Milton Talukder 1,  Shao-Shuai Bi 2,  Hai-Tao Jin 3,  Jing Ge 2,  Cong Zhang 4,  Mei-Wei Lv 2,  Jin-Long Li 5
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China; Department of Physiology and Pharmacology, Faculty of Animal Science and Veterinary Medicine, Patuakhali Science and Technology University, Barishal, 8210, Bangladesh.
  • 2 College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China.
  • 3 Quality and Safety Institute of Agricultural Products, Heilongjiang Academy of Agricultural Sciences, Harbin, 150010, China.
  • 4 College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China; College of Animal Science and Veterinary Medicine, Henan Agricultural University, 450046, Zhengzhou, Henan, China.
  • 5 College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin, 150030, China; Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Northeast Agricultural University, Harbin, 150030, China. Electronic address: [email protected].
PMID: 33965856 DOI: 10.1016/j.envpol.2021.117083
Abstract

Metal-responsive transcription factor 1 (MTF1) participates in redox homeostasis and heavy metals detoxification via regulating the expression of metal responsive genes. However, the exact role of MTF1 in Cd-induced cerebral toxicity remains unclear. Herein, we explored the mechanism of Cd-elicited cerebral toxicity through modulating MTF1/MTs pathway in chicken cerebrum exposed to different concentrations of Cd (35 mg, 70 mg, and 140 mg/kg CdCl2) via diet. Notably, cerebral tissues showed varying degrees of microstructural changes under Cd exposure. Cd exposure significantly up-regulated the expression of metal transporters (DMT1, ZIP8, and ZIP10) with concomitant elevated Cd level, as determined by ICP-MS. Cd significantly altered Other cerebral biometals concentrations (particularly, Zn, Fe, Se, Cr, Mo, and Pb) and redox balance, resulting in increased cerebral oxidative stress. More importantly, Cd exposure suppressed MTF1 mRNA and nuclear protein levels and its target metal-responsive genes, notably metallothioneins (MT1 and MT2), and Fe and Cu transporter genes (FPN1, ATOX1, and XIAP). Moreover, Cd disrupted the regulation of expression of selenoproteome (particularly, GPxs and SelW), and cerebral Se level. Overall, our data revealed that molecular mechanisms associated with Cd-induced cerebral damage might include over-expression of DMT1, ZIP8 and ZIP10, and suppression of MTF1 and its main target metal-responsive genes as well as several selenoproteins.

Keywords

Cadmium; Cerebral damage; MTF1; Metal transporters; Oxidative stress.

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