PMID- 28347754
OWN - NLM
STAT- MEDLINE
DCOM- 20170615
LR  - 20211204
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Linking)
VI  - 383
DP  - 2017 May 15
TI  - Cadmium disrupts autophagic flux by inhibiting cytosolic Ca(2+)-dependent 
      autophagosome-lysosome fusion in primary rat proximal tubular cells.
PG  - 13-23
LID - S0300-483X(17)30093-8 [pii]
LID - 10.1016/j.tox.2017.03.016 [doi]
AB  - Previous studies have shown that subcellular Ca(2+) redistribution is involved in 
      Cd-induced autophagy inhibition in primary rat proximal tubular (rPT) cells, but 
      the mechanism remains unclear. In this study, the status of autophagic flux was 
      monitored by the GFP and RFP tandemly tagged LC3 method. Pharmacological 
      inhibition of cytosolic Ca(2+) concentration ([Ca(2+)](c)) with 2-APB or BAPTA-AM 
      significantly alleviated Cd-elevated yellow puncta formation and restored 
      Cd-inhibited red puncta formation, while thapsigargin (TG) had the opposite 
      regulatory effect, demonstrating that Cd-induced [Ca(2+)](c) elevation inhibited 
      the autophagic flux in rPT cells. Resultantly, Cd-induced autophagosomes 
      accumulation was obviously modulated by 2-APB, BAPTA-AM and TG, respectively. 
      Meanwhile, blockage of autophagosome-lysosome fusion and decreased recruitment of 
      Rab7 to autophagosomes by Cd exposure was noticeably restored by 2-APB or 
      BAPTA-AM, but co-treatment with Cd and TG further impaired Cd-induced autophagy 
      arrest. Moreover, Cd-induced oxidative stress intimately correlated with 
      cytosolic Ca(2+) mobilization, and N-acetylcysteine (NAC) markedly rescued 
      Cd-blocked autophagosome-lysosome fusion and recruitment of Rab7 to 
      autophagosomes in rPT cells, implying that Cd-induced autophagy inhibition was 
      due to [Ca(2+)](c) elevation-triggered oxidative stress. In summary, these 
      results suggest that Cd-mediated autophagy inhibition in rPT cells is dependent 
      on cytosolic Ca(2+) overload. Elevation of [Ca(2+)](c) inhibited the 
      autophagosome-lysosome fusion to block the degradation of autophagosomes, which 
      aggravated Cd-induced cytotoxicity in rPT cells.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Liu, Fei
AU  - Liu F
AD  - College of Animal Science and Veterinary Medicine, Shandong Agricultural 
      University, Daizong Road No. 61, Tai'an 271018, People's Republic of China.
FAU - Wang, Xin-Yu
AU  - Wang XY
AD  - College of Animal Science and Veterinary Medicine, Shandong Agricultural 
      University, Daizong Road No. 61, Tai'an 271018, People's Republic of China.
FAU - Zhou, Xu-Ping
AU  - Zhou XP
AD  - Beijing University of Agriculture, Beijing 102206, People's Republic of China.
FAU - Liu, Zong-Ping
AU  - Liu ZP
AD  - College of Veterinary Medicine, Yangzhou University, 12 East Wenhui Road, 
      Yangzhou 225009, People's Republic of China. Electronic address: 
      liuzongping@yzu.edu.cn.
FAU - Song, Xiang-Bin
AU  - Song XB
AD  - College of Animal Science and Veterinary Medicine, Shandong Agricultural 
      University, Daizong Road No. 61, Tai'an 271018, People's Republic of China.
FAU - Wang, Zhen-Yong
AU  - Wang ZY
AD  - College of Animal Science and Veterinary Medicine, Shandong Agricultural 
      University, Daizong Road No. 61, Tai'an 271018, People's Republic of China.
FAU - Wang, Lin
AU  - Wang L
AD  - College of Animal Science and Veterinary Medicine, Shandong Agricultural 
      University, Daizong Road No. 61, Tai'an 271018, People's Republic of China. 
      Electronic address: wanglin2013@sdau.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20170325
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (LC3 protein, rat)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (rab7 GTP-Binding Proteins)
RN  - 0 (rab7 GTP-binding proteins, rat)
RN  - 00BH33GNGH (Cadmium)
RN  - EC 3.6.5.2 (rab GTP-Binding Proteins)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Autophagosomes/drug effects
MH  - Autophagy/*drug effects
MH  - Cadmium/*toxicity
MH  - Calcium/metabolism
MH  - Cells, Cultured
MH  - Cytosol/metabolism
MH  - Kidney Tubules, Proximal/*cytology
MH  - Lysosomes/drug effects
MH  - Male
MH  - Microtubule-Associated Proteins/metabolism
MH  - RNA-Binding Proteins/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - rab GTP-Binding Proteins/metabolism
MH  - rab7 GTP-Binding Proteins
OTO - NOTNLM
OT  - Autophagosome-lysosome fusion
OT  - Autophagy
OT  - Cadmium
OT  - Cytosolic calcium overload
OT  - Oxidative stress
OT  - Proximal tubular cells
EDAT- 2017/03/30 06:00
MHDA- 2017/06/16 06:00
CRDT- 2017/03/29 06:00
PHST- 2017/01/22 00:00 [received]
PHST- 2017/03/08 00:00 [revised]
PHST- 2017/03/14 00:00 [accepted]
PHST- 2017/03/30 06:00 [pubmed]
PHST- 2017/06/16 06:00 [medline]
PHST- 2017/03/29 06:00 [entrez]
AID - S0300-483X(17)30093-8 [pii]
AID - 10.1016/j.tox.2017.03.016 [doi]
PST - ppublish
SO  - Toxicology. 2017 May 15;383:13-23. doi: 10.1016/j.tox.2017.03.016. Epub 2017 Mar 
      25.