PMID- 31710081
OWN - NLM
STAT- MEDLINE
DCOM- 20200923
LR  - 20200923
IS  - 1573-4935 (Electronic)
IS  - 0144-8463 (Print)
IS  - 0144-8463 (Linking)
VI  - 39
IP  - 12
DP  - 2019 Dec 20
TI  - Endoplasmic reticulum Ca2+ release causes Rieske iron-sulfur protein-mediated 
      mitochondrial ROS generation in pulmonary artery smooth muscle cells.
LID - 10.1042/BSR20192414 [doi]
LID - BSR20192414
AB  - Mitochondrial reactive oxygen species (ROS) cause Ca2+ release from the 
      endoplasmic reticulum (ER) via ryanodine receptors (RyRs) in pulmonary artery 
      smooth muscle cells (PASMCs), playing an essential role in hypoxic pulmonary 
      vasoconstriction (HPV). Here we tested a novel hypothesis that hypoxia-induced 
      RyR-mediated Ca2+ release may, in turn, promote mitochondrial ROS generation 
      contributing to hypoxic cellular responses in PASMCs. Our data reveal that 
      application of caffeine to elevate intracellular Ca2+ concentration ([Ca2+]i) by 
      activating RyRs results in a significant increase in ROS production in cytosol 
      and mitochondria of PASMCs. Norepinephrine to increase [Ca2+]i due to the opening 
      of inositol 1,4,5-triphosphate receptors (IP3Rs) produces similar effects. 
      Exogenous Ca2+ significantly increases mitochondrial-derived ROS generation as 
      well. Ru360 also inhibits the hypoxic ROS production. The RyR antagonist 
      tetracaine or RyR2 gene knockout (KO) suppresses hypoxia-induced responses as 
      well. Inhibition of mitochondrial Ca2+ uptake with Ru360 eliminates N- and 
      Ca2+-induced responses. RISP KD abolishes the hypoxia-induced ROS production in 
      mitochondria of PASMCs. Rieske iron-sulfur protein (RISP) gene knockdown (KD) 
      blocks caffeine- or NE-induced ROS production. Taken together, these findings 
      have further demonstrated that ER Ca2+ release causes mitochondrial Ca2+ uptake 
      and RISP-mediated ROS production; this novel local ER/mitochondrion 
      communication-elicited, Ca2+-mediated, RISP-dependent ROS production may play a 
      significant role in hypoxic cellular responses in PASMCs.
CI  - (c) 2019 The Author(s).
FAU - Dong, Dapeng
AU  - Dong D
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Wenzhou Medical University, Wenzhou 325000, China.
FAU - Hao, Qiongyu
AU  - Hao Q
AD  - Division of Cancer Research and Training, Department of Internal Medicine, 
      Charles Drew University of Medicine and Science, Los Angeles, CA 90059, U.S.A.
AD  - David Geffen UCLA School of Medicine and UCLA Jonsson Comprehensive Cancer 
      Center, Los Angeles, CA 90095, U.S.A.
FAU - Zhang, Ping
AU  - Zhang P
AD  - Radiation and Medical Oncology Department, The 1st Affiliated Hospital of Wenzhou 
      Medical University, Wenzhou 325000, China.
FAU - Wang, Tao
AU  - Wang T
AD  - The Key Laboratory of Urinary Tract Tumors and Calculi, Department of Urology 
      Surgery, The First Affiliated Hospital of Xiamen University, Xiamen 361003, 
      China.
FAU - Han, Fei
AU  - Han F
AD  - Division of Radiological Sciences, Washington University School of Medicine in 
      Saint Louis, MO 63110, U.S.A.
AD  - Department of Pathology, Tongji Hospital, Tongji University School of Medicine, 
      Shanghai 200065, China.
FAU - Liang, Xiaodong
AU  - Liang X
AD  - Department of Pathology, Yancheng Hospital Affiliated Southeast University, 
      Yancheng, Jiangsu 224000, China.
FAU - Fei, Zhenghua
AU  - Fei Z
AD  - Radiation and Medical Oncology Department, The 1st Affiliated Hospital of Wenzhou 
      Medical University, Wenzhou 325000, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Retracted Publication
PL  - England
TA  - Biosci Rep
JT  - Bioscience reports
JID - 8102797
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Rieske iron-sulfur protein)
RN  - EC 7.1.1.8 (Electron Transport Complex III)
RN  - SY7Q814VUP (Calcium)
SB  - IM
RIN - Biosci Rep. 2020 Apr 30;40(4):. PMID: 32324243
MH  - Animals
MH  - Calcium/*metabolism
MH  - Electron Transport Complex III/genetics/*metabolism
MH  - Endoplasmic Reticulum/genetics/*metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Mitochondria/genetics/*metabolism/pathology
MH  - Mitochondrial Proteins/genetics/*metabolism
MH  - Muscle, Smooth, Vascular/*metabolism/pathology
MH  - Myocytes, Smooth Muscle/*metabolism/pathology
MH  - Pulmonary Artery/*metabolism/pathology
MH  - Reactive Oxygen Species/*metabolism
PMC - PMC6893167
OTO - NOTNLM
OT  - Intracellular calcium
OT  - Ryanodine receptor
OT  - mitochondrial ROS
COIS- The authors declare that there are no competing interests associated with the 
      manuscript.
EDAT- 2019/11/12 06:00
MHDA- 2020/09/24 06:00
PMCR- 2019/12/04
CRDT- 2019/11/12 06:00
PHST- 2019/08/01 00:00 [received]
PHST- 2019/10/30 00:00 [revised]
PHST- 2019/11/07 00:00 [accepted]
PHST- 2019/11/12 06:00 [pubmed]
PHST- 2020/09/24 06:00 [medline]
PHST- 2019/11/12 06:00 [entrez]
PHST- 2019/12/04 00:00 [pmc-release]
AID - 221066 [pii]
AID - BSR20192414 [pii]
AID - 10.1042/BSR20192414 [doi]
PST - ppublish
SO  - Biosci Rep. 2019 Dec 20;39(12):BSR20192414. doi: 10.1042/BSR20192414.