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Protective function of SLC30A10 induced via PERK-ATF4 pathway against 1-methyl-4-phenylpyridinium

Suzuna Go1, Hisaka Kurita1, Kazuki Yokoo1

  • 1Laboratory of Medical Therapeutics and Molecular Therapeutics, Department Biomedical Pharmaceutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi Gifu City, Gifu 501-1196, Japan.

Biochemical and Biophysical Research Communications
|July 10, 2017
PubMed

Insights

Solute carrier family 30 member 10 (SLC30A10) protects against 1-methyl-4-phenylpiridium ion (MPP+) induced neurotoxicity. This manganese transporter is upregulated via ER stress and the PERK-ATF4 pathway, mitigating cellular damage.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Neurodegenerative diseases are linked to cellular stress, including oxidative and endoplasmic reticulum (ER) stress.
  • The role of manganese transporter Solute Carrier Family 30 Member 10 (SLC30A10) in intracellular stress responses remains unclear.
  • Slc30a10 levels increase in the midbrain of MPTP-treated mice, suggesting a potential role in neurotoxicity.

Purpose of the Study:

  • To investigate the involvement of SLC30A10 in 1-methyl-4-phenylpiridium ion (MPP+)-induced intracellular stress.
  • To elucidate the molecular mechanism underlying SLC30A10 induction by MPP+ treatment.
  • To determine the protective role of SLC30A10 against MPP+-induced neurotoxicity.

Main Methods:

  • MPP+ treatment of human neuroblastoma SH-SY5Y cells.
  • Analysis of SLC30A10 and ER stress marker (CHOP) mRNA levels.
  • Tunicamycin treatment to induce ER stress.
  • Investigation of the PERK-ATF4 pathway, including ATF4 knockdown.
  • Cell viability assays in SLC30A10 knockdown cells.

Main Results:

  • MPP+ treatment significantly increased SLC30A10 and CHOP mRNA levels in SH-SY5Y cells.
  • ER stress induced by tunicamycin also upregulated SLC30A10 mRNA, suggesting MPP+ acts via ER stress.
  • SLC30A10 induction by MPP+ was dependent on the PERK-ATF4 pathway, as ATF4 knockdown abolished the increase.
  • SLC30A10 knockdown exacerbated MPP+-induced ER stress and reduced cell viability.

Conclusions:

  • SLC30A10 is upregulated in response to MPP+-induced ER stress through the PERK-ATF4 pathway.
  • SLC30A10 plays a protective role against MPP+-induced neurotoxicity by mitigating ER stress.
  • These findings highlight SLC30A10 as a potential therapeutic target for neurodegenerative conditions involving ER stress.
Keywords:
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine1-Methyl-4-phenylpiridium ionATF4Endoplasmic reticulum stressParkinson's diseaseSLC30A10

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