TRPC6-Mediated Ca2+ Signaling is Required for Hypoxia-Induced Autophagy in Human Podocytes

被引:16
|
作者
Ji, Tianrong [1 ]
Zhang, Chengwei [1 ]
Ma, Linlin [1 ]
Wang, Qin [1 ]
Zou, Li [1 ]
Meng, Kexin [1 ]
Zhang, Rui [1 ]
Jiao, Jundong [1 ,2 ]
机构
[1] Harbin Med Univ, Affiliated Hosp 2, Dept Nephrol, Harbin, Heilongjiang, Peoples R China
[2] Harbin Med Univ, Inst Nephrol, Harbin, Heilongjiang, Peoples R China
关键词
Trpc6; Podocytes; Autophagy; Ca2+ signaling; Adenosine monophosphate-activated protein kinase; KINASE KINASE-BETA; AMPK ACTIVATION; TRPC6; CHANNELS; CAMKK-BETA; CALCIUM; PATHWAY; CELLS; MACROAUTOPHAGY; INDUCTION; DISEASE;
D O I
10.1159/000492351
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Background/Aims: Intracellular Ca2+ signaling plays an important role in the regulation of autophagy. However, very little is known about the role of Ca2+ influx, which is induced by plasma membrane Ca2+ channels. Our previous study showed that transient receptor potential canonical channel-6 (TRPC6), a major Ca2+ influx pathway in podocytes, was activated by hypoxia. Here, we investigated whether TRPC6 is involved in hypoxia-induced autophagy in cultured human podocytes. Methods: In the present study, an immortalized human podocyte cell line was used. Fluo-3 fluorescence was utilized to determine intracellular Ca2+ concentration ([Ca2+](i)), and western blotting was used to measure autophagy and protein expression. Results: We found that blockade TRPC6 by using either TRPC6 siRNA or a TRPC6 blocker attenuated hypoxia-induced autophagy, while enhancement of TRPC6 activity with a TRPC6 activator enhanced hypoxia-induced autophagy. Furthermore, TRPC6-dependent Ca2+ signaling is responsible for hypoxia-induced autophagy since both an intracellular and extracellular Ca2+ chelator abolished hypoxia-induced autophagy. Moreover, we found that blockade of TRPC6 by using either TRPC6 siRNA or a TRPC6 blocker decreased the expression of adenosine monophosphate-activated protein kinase (AMPK), an important signaling molecule in Ca2+-dependent autophagy activation, which is activated under hypoxic conditions. These data suggest that the involvement of TRPC6 in hypoxia-induced autophagy is associated with AMPK signaling. Conclusion: TRPC6 is essential for hypoxia-induced autophagy in podocytes. (c) 2018 The Author(s) Published by S. Karger AG, Basel
引用
收藏
页码:1782 / 1792
页数:11
相关论文
共 50 条
  • [41] TRPC3 is an essential determinant of VEGF-mediated Ca2+ signaling in proliferating endothelial progenitor cells
    Krenn, Martin
    Graziani, Annarita
    Poteser, Michael
    Eder, Petra
    Trantina-Yates, Ameli
    Muechler, Heinrich
    Romanin, Christoph
    Groschner, Klaus
    BIOPHYSICAL JOURNAL, 2007, : 290A - 290A
  • [42] Evidence against a major role for Ca2+ in hypoxia-induced gene expression in human hepatoma cells (Hep3B)
    Metzen, E
    Fandrey, J
    Jelkmann, W
    JOURNAL OF PHYSIOLOGY-LONDON, 1999, 517 (03): : 651 - 657
  • [43] Diacylglycerol-mediated Ca2+ influx through TRPC3/6 is essential for Angiotensin II-induced cardiac hypertrophy
    Nishida, Motohiro
    Onohara, Naoya
    Kurose, Hitoshi
    JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2006, 41 (06) : 1046 - 1046
  • [44] Hydrogen Sulfide Protects against Chemical Hypoxia-Induced Injury via Attenuation of ROS-Mediated Ca2+ Overload and Mitochondrial Dysfunction in Human Bronchial Epithelial Cells
    Liu, Cai-Xia
    Tan, Yu-Rong
    Xiang, Yang
    Liu, Chi
    Liu, Xiao-Ai
    Qin, Xiao-Qun
    BIOMED RESEARCH INTERNATIONAL, 2018, 2018
  • [45] POSSIBLE ROLE OF TRPC1-MEDIATED Ca2+ ENTRY IN DECIDUALIZATION OF HUMAN ENDOMETRIAL STROMAL CELLS
    Kawarabayashi, Yasuhiro
    Hai, Lin
    Honda, Akira
    Mori, Masayuki X.
    Hatae, Junna
    Inoue, Ryuji
    JOURNAL OF PHYSIOLOGICAL SCIENCES, 2009, 59 : 229 - 229
  • [46] Critical Role of TRPC1-Mediated Ca2+ Entry in Decidualization of Human Endometrial Stromal Cells
    Kawarabayashi, Yasuhiro
    Hai, Lin
    Honda, Akira
    Horiuchi, Shinji
    Tsujioka, Hiroshi
    Ichikawa, Jun
    Inoue, Ryuji
    MOLECULAR ENDOCRINOLOGY, 2012, 26 (05) : 846 - 858
  • [47] Intracellular Ca2+ signaling is required for neurotrophin-induced potentiation in the adult rat hippocampus
    Kang, HJ
    Schuman, EM
    NEUROSCIENCE LETTERS, 2000, 282 (03) : 141 - 144
  • [48] Astrocytic IP3-mediated Ca2+ signaling is required for functional integrity of tripartite synapse
    Tanaka, Mika
    Gomi, Hiroshi
    Nakai, Junichi
    Lebedinskiy, Alexander
    Shih, Pei-Yu
    Ando, Reiko
    Mikoshiba, Katsuhiko
    Semyanov, Alexey
    Itohara, Shigeyoshi
    NEUROSCIENCE RESEARCH, 2010, 68 : E243 - E243
  • [49] Role of BK in hypoxia-induced elevation of [Ca2+]i in depolarized rat carotid body glomus cells
    Wang, Jiaju
    Hogan, James O.
    Kim, Donghee
    FASEB JOURNAL, 2016, 30
  • [50] Reduction of TRPC1/TRPC3 mediated Ca2+-signaling protects oxidative stress-induced COPD
    Shin, Samuel
    Gombedza, Farai C.
    Boadi, Eugenia Awuah
    Yiu, Allen J.
    Roy, Sanjit K.
    Bandyopadhyay, Bidhan C.
    CELLULAR SIGNALLING, 2023, 107