title: A novel role of transient receptor potential mucolipin1 (TRPML1) in protecting against imidazole-induced cytotoxicity.
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.
authors: a Laboratory of Animal Embryonic Biotechnology, College of Animal Science and Technology, China Agricultural University, Beijing 100193, P.R. China.
authors: Zhenxing
authors: Z
authors: Liu
authors: Shuan
authors: S
authors: Zhao
authors: Shuaishuai
authors: S
authors: Wu
authors: Jingyou
authors: J
authors: Zhang
authors: Zunyang
authors: Z
authors: Nie
authors: Shenming
authors: S
authors: Zeng
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000494:pharmacology*; D008247:Lysosomes / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000502:physiology*; D014617:Vacuoles / Q000378:metabolism
chemical_list: D007093:Imidazoles; C416674:MCOLN1 protein, human; D050051:Transient Receptor Potential Channels; C029899:imidazole
keywords: TRPML1; cell death; cytoplasmic vacuolation; imidazole; lysosomal pH; mort cellulaire; pH du lysosome; vacuolisation cytoplasmique