Heat stress induces apoptosis through transcription-independent p53-mediated mitochondrial pathways in human umbilical vein endothelial cell

Gu, Zhengtao; Wang, H.; Li, L.; Liu, Y. S.; Deng, Xian-Yu; Huo, ShouJun; Yuan, Fangfang; Liu, Z. F.; Tong, Huasheng; Su, Lei

doi:10.1038/srep04469

Cited by 122 publications

(101 citation statements)

References 54 publications

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“…Previous studies have suggested that bronchial epithelial cells are early targets of thermal inhalation injury [2]. Most studies have focused on the bronchial epithelial inflammation induced by chemical smoke or heat, ignoring that heat can also induce cell apoptosis and death, contributing to the inhalation injury [3]. Heat is a major extracellular stimulus that causes cellular oxidative stress and apoptosis [4].…”

Section: Introductionmentioning

confidence: 99%

Curcumin Inhibits Heat-Induced Apoptosis by Suppressing NADPH Oxidase 2 and Activating the Akt/mTOR Signaling Pathway in Bronchial Epithelial Cells

Yuan

Tang

et al. 2017

Cell Physiol Biochem

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Background: Heat causes bronchial epithelial cell apoptosis, which is a known factor contributing to airway damage during inhalation injury. Accumulating evidence has shown the effect of curcumin on inhibiting apoptosis. In this study, we investigated whether curcumin suppresses heat-induced apoptosis in bronchial epithelial cells and the underlying mechanism. Methods: Bronchial epithelial cell line 16HBE140 cells were incubated at either 42 °C, 47 °C, 52 °C, or 57 °C for 5 min in a cell incubator and then returned back to normal culture conditions (37 °C). An in vivo thermal inhalation injury rat model was established with a heat gun blowing hot air into the airway of rats. 16HBE140 cells and lung tissue were obtained for further study with or without curcumin treatment. Cell viability was determined by measuring the absorbance of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). 2',7'-dichlorofluorescein diacetate fluorescence was used as a measure of reactive oxygen species (ROS) production. Levels of Bcl2, Bax, α-ATP, cleaved Poly (ADP-ribose) polymerase (PARP), cleaved caspase-3, gp91^phox, p47^phox, p67^phox, p22^phox, p40^phox, and Rac were determined by Western blotting. TUNEL staining was used to determine apoptosis. Results: Heat treatment triggered the apoptosis of 16HBE140 cells as shown by the increase in apoptosis molecular markers, including Bcl-2, Bax, cleaved PARP, and cleaved caspase-3. Administration of curcumin significantly inhibited apoptosis of 16HBE140 cells and suppressed the membrane translocation of NADPH oxidase 2 cytosolic components, as well as ROS production. Downregulation of Akt and mTOR phosphorylation induced by heat was also reversed by curcumin. Furthermore, we demonstrated that NADPH oxidase 2 is upstream of Akt/mTOR in heat-induced apoptosis. The protective role of curcumin on bronchial epithelia apoptosis was also confirmed in vivo by a rat inhalation injury model. Conclusion: This study demonstrates that one of the critical mechanisms underlying curcumin inhibiting heat-induced apoptosis is through suppressing NADPH Oxidase 2 and activating the Akt/mTOR signaling pathway in bronchial epithelial cells.

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Section: Introductionmentioning

confidence: 99%

Curcumin Inhibits Heat-Induced Apoptosis by Suppressing NADPH Oxidase 2 and Activating the Akt/mTOR Signaling Pathway in Bronchial Epithelial Cells

Yuan

Tang

et al. 2017

Cell Physiol Biochem

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“…This temperature rise is considered to have little influence on endothelial cells. This notion is supported by the report that the viability of HUVECs was not affected by heat stress at 39°C [20]. The micropower plasma can expose living cells to various reactive chemical species without harmful effects of heat and change in pH, in comparison with the plasma at the gas-liquid interface used in the previous studies [9–14].…”

Section: Discussionsupporting

confidence: 52%

Proliferation-Related Activity in Endothelial Cells Is Enhanced by Micropower Plasma

Suzuki

Yoshino

2016

BioMed Research International

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Nonthermal plasma has received a lot of attention as a medical treatment technique in recent years. It can easily create various reactive chemical species (ROS) and is harmless to living body. Although plasma at gas-liquid interface has a potential for a biomedical application, the interactions between the gas-liquid plasma and living cells remain unclear. Here, we show characteristics of a micropower plasma with 0.018 W of the power input, generated at gas-liquid interface. We also provide the evidence of plasma-induced enhancement in proliferation activity of endothelial cells. The plasma produced H2O2, HNO2, and HNO3 in phosphate buffered saline containing Mg++ and Ca++ (PBS(+)), and their concentration increased linearly during 600-second discharge. The value of pH in PBS(+) against the plasma discharge time was stable at about 7.0. Temperature in PBS(+) rose monotonically, and its rise was up to 0.8°C at the bottom of a cell-cultured dish by the plasma discharge for 600 s. Short-time treatment of the plasma enhanced proliferation activity of endothelial cells. In contrast, the treatment of H2O2 does not enhance the cell proliferation. Thus, the ROS production and the nuclear factor-kappa B (NF-κB) activation due to the plasma treatment might be related to enhancement of the cell proliferation. Our results may potentially provide the basis for developing the biomedical applications using the gas-liquid plasma.

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“…Taken together, the activation of several cancer pathways and the expression of the tumor suppressors, the cell cycle arrestors, along with the activation of such a large number of genes involved in apoptosis and the expression of large number of genes belonging to macrophage lineage (Table 5) suggests that severe cell anomaly and DNA damage has taken place due to thermal stress. Gu et al (2014) recently showed that HS can induce apoptosis by activating p53-mediated mitochondrial pathways; three genes involved in p53 signaling pathway (CASP8, MDM-X, and CYCLIN G) were differentially expressed in this study. Several genes, such as FADD, CASP8, BRIC4, JUN, PI3K, and AKT3, which play a critical role in inducing apoptosis through TNF and PI3K-Akt signaling pathways, were also differentially expressed.…”

Section: Apoptosismentioning

confidence: 95%

Characterization of genes and pathways that respond to heat stress in Holstein calves through transcriptome analysis

Srikanth

Kwon

Lee

2017

Cell Stress and Chaperones

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This study aimed to investigate the genes and pathways that respond to heat stress in Holstein bull calves exposed to severe ranges of temperature and humidity. A total of ten animals from 4 to 6 months of age were subjected to heat stress at 37°C and 90 % humidity for 12 h. Skin and rectal temperatures were measured before and after heat stress; while no correlation was found between them before heat stress, a moderate correlation was detected after heat stress, confirming rectal temperature to be a better barometer for monitoring heat stress. RNAseq analysis identified 8567 genes to be differentially regulated, out of which 465 genes were significantly upregulated (≥2-fold, P < 0.05) and 49 genes were significantly downregulated (≤2-fold, P < 0.05) in response to heat stress. Significant terms and pathways enriched in response to heat stress included chaperones, cochaperones, cellular response to heat stress, phosphorylation, kinase activation, immune response, apoptosis, Toll-like receptor signaling pathway, Pi3K/AKT activation, protein processing in endoplasmic reticulum, interferon signaling, pathways in cancer, estrogen signaling pathway, and MAPK signaling pathway. The differentially expressed genes were validated by quantitative realtime PCR analysis, which confirmed the tendency of the expression. The genes and pathways identified in this analysis extend our understanding of transcriptional response to heat stress and their likely functioning in adapting the animal to hyperthermic stress. The identified genes could be used as candidate genes for association studies to select and breed animals with improved heat tolerance.

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Heat stress induces apoptosis through transcription-independent p53-mediated mitochondrial pathways in human umbilical vein endothelial cell

Cited by 122 publications

References 54 publications

Curcumin Inhibits Heat-Induced Apoptosis by Suppressing NADPH Oxidase 2 and Activating the Akt/mTOR Signaling Pathway in Bronchial Epithelial Cells

Curcumin Inhibits Heat-Induced Apoptosis by Suppressing NADPH Oxidase 2 and Activating the Akt/mTOR Signaling Pathway in Bronchial Epithelial Cells

Proliferation-Related Activity in Endothelial Cells Is Enhanced by Micropower Plasma

Characterization of genes and pathways that respond to heat stress in Holstein calves through transcriptome analysis

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