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A novel role of transient receptor potential mucolipin1 (TRPML1) in protecting against imidazole-induced cytotoxicity
- Source :
- Biochemistry and cell biology = Biochimie et biologie cellulaire. 92(4)
- Publication Year :
- 2014
-
Abstract
- Lysosomotropic amines cause serious side effects such as cytoplasmic vacuolation and cell death. TRPML1 (also known as mucolipin1), a member of the transient receptor potential (TRP) protein family, may regulate fusion/fission of vesicles along the endocytic pathway and some aspects of lysosomal ion homeostasis. Nevertheless, it is still unknown whether TRPML1 is involved in death of mammalian cells induced by lysosomotropic agents. In this study, imidazole was used as a model to investigate the role of TRPML1 in the cytotoxicity of lysosomotropic agents. Overexpression of wild-type TRPML1 inhibited imidazole-induced vacuole formation and cell death in human endometrial adenocarcinoma (HEC-1B) cells. In contrast, siRNA-mediated TRPML1 knockdown increased the cell death induced by imidazole. Bafilomycin A1 raises the pH of acidic organelles and therefore suppresses accumulation of weak bases in them. Similarly, lysosomal pH was raised in TRPML1-overexpressing cells; therefore, we inferred that TRPML1 protected against imidazole toxicity by regulating the pH of acidic organelles. We concluded that TRPML1 had a novel role in protecting against lysosomotropic amine toxicity.
- Subjects :
- Programmed cell death
Protein family
Imidazoles
Apoptosis
Cell Biology
Biology
Hydrogen-Ion Concentration
Biochemistry
Cell biology
Transient receptor potential channel
chemistry.chemical_compound
Transient Receptor Potential Channels
chemistry
Cell Line, Tumor
Gene Knockdown Techniques
Vacuoles
Imidazole
Humans
Cytotoxicity
Lysosomes
Molecular Biology
Cytoplasmic Vacuolation
Subjects
Details
- ISSN :
- 12086002
- Volume :
- 92
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Biochemistry and cell biology = Biochimie et biologie cellulaire
- Accession number :
- edsair.doi.dedup.....249a966022bdcf4aac3c8a5c6ad013c8