TRPC1 expression and function inhibit ER stress and cell death in salivary gland cells

Pramod Sukumaran, Yuyang Sun, Fredice Quenum Zangbede, Viviane Nascimento da Conceicao, Bibhuti Mishra, Brij B. Singh

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Disturbances in endoplasmic reticulum (ER) Ca2+ homeostasis have been associated with many diseases including loss of salivary glands. Although significant progress has been accomplished which led to the increase in our understanding of the cellular responses to ER stress, the factors/ion channels that could inhibit ER stress are not yet identified. Here, we show that TRPC1 (transient receptor potential canonical 1) is involved in regulating Ca2+ homeostasis and loss of TRPC1 decreased ER Ca2+ levels, inhibited the unfolded protein response (UPR), that induced loss of salivary gland cells. We provide further evidence that ER stress-inducing agents (Tunicamycin [Tu] and Brefeldin A [BFA]) disrupt Ca2+ homeostasis by directly inhibiting TRPC1-mediated Ca2+ entry, which led to ER stress in salivary gland cells. Moreover, induction of ER stress lead to an increase in C/EBP homologous protein (CHOP) expression, which decreased TRPC1 expression and subsequently attenuated autophagy along with increased apoptosis. Importantly, TRPC1−/− mice showed increased ER stress, increased immune cell infiltration, loss of Ca2+ homeostasis, decreased saliva secretion, and decreased salivary gland survival. Finally, restoration of TRPC1 not only maintained Ca2+ homeostasis but also inhibited ER stress that induced cell survival. Overall these results suggest a significant role of TRPC1 Ca2+ channels in ER stress and homeostatic function/survival of salivary gland cells.

Original languageEnglish (US)
Pages (from-to)40-50
Number of pages11
JournalFASEB BioAdvances
Volume1
Issue number1
DOIs
StatePublished - Jan 2019

Keywords

  • ER stress
  • SOCE
  • TRPC1
  • Tunicamycin
  • salivary gland

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Cancer Research
  • Molecular Medicine
  • Physiology

Fingerprint

Dive into the research topics of 'TRPC1 expression and function inhibit ER stress and cell death in salivary gland cells'. Together they form a unique fingerprint.

Cite this