Curcumin facilitates a transitory cellular stress response in trembler-J mice

Yuji Okamoto, Davut Pehlivan, Wojciech Wiszniewski, Christine R. Beck, G. Jackson Snipes, James R. Lupski, Mehrdad Khajavi

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

We have previously shown that oral administration of curcumin significantly decreases the percentage of apoptotic Schwann cells and partially mitigates the severe neuropathy phenotype of the Trembler-J (Tr-J)mouse model in a dose-dependent manner.Here we compared the gene expression in sciatic nerves of 2-week-old pup sand adult Tr-J with the sameage groups of wild-type mice and found a significant increase ingene expression for hypoxia, inflammatory response and heat-shock proteins, the latter specifically the Hsp70 family, in Tr-J mice.Wealso detected an activation of different branches of unfolded protein responses (UPRs) in Tr-J mice. Administering curcumin results in lower expression of UPR markers suggesting it relieves endoplasmic reticulum (ER) cell stress sensorsin sciatic nervesof Tr-Jmicewhile the level of heat-shock proteins stays comparable to untreated Tr-Jmice. We further tested if Hsp70 levels could influence the severity of the Tr-J neuropathy. Notably, reduced dosage of the Hsp70 strongly potentiates the severity of the Tr-J neuropathy, though the absence of Hsp70 had little effect in wild-type mice. In aggregate, these data provide further insights into the pathological disease mechanisms caused by myelin genemutations and further support the exploration of curcumin as a therapeutic approach for selected forms of inherited neuropathy and potentially for other genetic diseases due to ER-retained mutants.

Original languageEnglish (US)
Article numberddt318
Pages (from-to)4698-4705
Number of pages8
JournalHuman molecular genetics
Volume22
Issue number23
DOIs
StatePublished - Dec 2013

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Okamoto, Y., Pehlivan, D., Wiszniewski, W., Beck, C. R., Jackson Snipes, G., Lupski, J. R., & Khajavi, M. (2013). Curcumin facilitates a transitory cellular stress response in trembler-J mice. Human molecular genetics, 22(23), 4698-4705. [ddt318]. https://doi.org/10.1093/hmg/ddt318