PMID- 27665314
OWN - NLM
STAT- MEDLINE
DCOM- 20170904
LR  - 20180312
IS  - 1873-3344 (Electronic)
IS  - 0162-0134 (Linking)
VI  - 164
DP  - 2016 Nov
TI  - Role of subcellular calcium redistribution in regulating apoptosis and autophagy 
      in cadmium-exposed primary rat proximal tubular cells.
PG  - 99-109
LID - S0162-0134(16)30251-3 [pii]
LID - 10.1016/j.jinorgbio.2016.09.005 [doi]
AB  - Ca(2+) signaling plays a vital role in regulating apoptosis and autophagy. We 
      previously proved that cytosolic Ca(2+) overload is involved in cadmium 
      (Cd)-induced apoptosis in rat proximal tubular (rPT) cells, but the source of 
      elevated cytosolic Ca(2+) concentration ([Ca(2+)](c)) and the effect of potential 
      subcellular Ca(2+) redistribution on apoptosis and autophagy remain to be 
      elucidated. Firstly, data showed that Cd-induced elevation of [Ca(2+)](c) was 
      primarily generated intracellularly. Moreover, elevations of [Ca(2+)](c) and 
      mitochondrial Ca(2+) concentration ([Ca(2+)](mit)) with depletion of endoplasmic 
      reticulum (ER) Ca(2+) levels ([Ca(2+)](ER)) were revealed in Cd-treated rPT 
      cells, but this subcellular Ca(2+) redistribution was significantly suppressed by 
      2-Aminoethoxydiphenyl borate (2-APB). Elevated inositol 1,4,5-trisphosphate 
      (IP(3)) levels with up-regulated IP(3) receptor (IP(3)R) protein levels were 
      shown in Cd-exposed cells, confirming that IP(3)R-mediated ER Ca(2+) release 
      results in the elevation of [Ca(2+)](c). Up-regulated sequestosome 1 (p62) 
      protein levels and autophagic flux assay demonstrated that Cd impaired autophagic 
      degradation, while N-acetylcysteine (NAC) markedly attenuated Cd-induced p62 and 
      microtubule-associated protein 1 light chain 3-II (LC3-II) accumulation, implying 
      that the inhibition of autophagic flux was due to oxidative stress. Furthermore, 
      pharmacological modulation of [Ca(2+)](c) with 1,2-Bis (2-aminophenoxy) 
      ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM) and 2-APB 
      alleviated Cd-mediated apoptosis, inhibition of autophagic degradation and 
      subsequent cytotoxicity, while thapsigargin (TG) had the opposite regulatory 
      effect on them. In summary, cytosolic calcium overload originated from 
      IP(3)R-mediated ER Ca(2+) release has a negative impact on Cd nephrotoxicity 
      through its promotion of apoptosis and inhibition of autophagic flux.
CI  - Copyright (c) 2016 Elsevier Inc. 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 - Li, Zi-Fa
AU  - Li ZF
AD  - Laboratory Animal Center of Shandong University of Traditional Chinese Medicine, 
      Jinan 250355, 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
PT  - Research Support, Non-U.S. Gov't
DEP - 20160914
PL  - United States
TA  - J Inorg Biochem
JT  - Journal of inorganic biochemistry
JID - 7905788
RN  - 00BH33GNGH (Cadmium)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Autophagy/*drug effects
MH  - Cadmium/*pharmacology
MH  - Calcium/*metabolism
MH  - Endoplasmic Reticulum/*metabolism
MH  - Kidney Tubules, Proximal/cytology/*metabolism
MH  - Rats
OTO - NOTNLM
OT  - Apoptosis
OT  - Autophagy
OT  - Cadmium
OT  - Cytosolic calcium overload
OT  - Endoplasmic reticulum
OT  - Proximal tubular cells
EDAT- 2016/09/26 06:00
MHDA- 2017/09/05 06:00
CRDT- 2016/09/26 06:00
PHST- 2016/06/13 00:00 [received]
PHST- 2016/08/30 00:00 [revised]
PHST- 2016/09/13 00:00 [accepted]
PHST- 2016/09/26 06:00 [pubmed]
PHST- 2017/09/05 06:00 [medline]
PHST- 2016/09/26 06:00 [entrez]
AID - S0162-0134(16)30251-3 [pii]
AID - 10.1016/j.jinorgbio.2016.09.005 [doi]
PST - ppublish
SO  - J Inorg Biochem. 2016 Nov;164:99-109. doi: 10.1016/j.jinorgbio.2016.09.005. Epub 
      2016 Sep 14.