Mitochondrial superoxide anions induced by exogenous oxidative stress determine tumor cell fate: an individual cell-based study.

J Zhejiang Univ Sci B 2019 Apr.;20(4):310-321

The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.

Objective: Reactive oxygen species (ROS) are involved in a variety of biological phenomena and serve both deleterious and beneficial roles. ROS quantification and assessment of reaction networks are desirable but difficult because of their short half-life and high reactivity. Here, we describe a pro-oxidative model in a single human lung carcinoma SPC-A-1 cell that was created by application of extracellular HO stimuli.

Methods: Modified microfluidics and imaging techniques were used to determine O levels and construct an O reaction network. To elucidate the consequences of increased O input, the mitochondria were given a central role in the oxidative stress mode, by manipulating mitochondria-interrelated cytosolic Ca levels, mitochondrial Ca uptake, auto-amplification of intracellular ROS and the intrinsic apoptotic pathway.

Results And Conclusions: Results from a modified microchip demonstrated that 1 mmol/L HO induced a rapid increase in cellular O levels (>27 vs. >406 amol in 20 min), leading to increased cellular oxidizing power (evaluated by ROS levels) and decreased reducing power (evaluated by glutathione (GSH) levels). In addition, we examined the dynamics of cytosolic Ca and mitochondrial Ca by confocal laser scanning microscopy and confirmed that Ca stores in the endoplasmic reticulum were the primary source of HO-induced cytosolic Ca bursts. It is clear that mitochondria have pivotal roles in determining how exogenous oxidative stress affects cell fate. The stress response involves the transfer of Ca signals between organelles, ROS auto-amplification, mitochondrial dysfunction, and a caspase-dependent apoptotic pathway.

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Source
http://dx.doi.org/10.1631/jzus.B1800319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454314PMC
September 2019
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