NO/cGMP/PKG activation protects Drosophila cells subjected to hypoxic stress

Mahneva, Olena; Caplan, Stacee Lee; Ivko, Polina; Milton, Sarah L.

doi:10.1016/j.cbpc.2019.05.013

Cited by 9 publications

(6 citation statements)

References 66 publications

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“…[ 40 ] A number of studies have shown that NO could act as a “second messenger” to regulate multiple intracellular downstream signal factors, such as soluble GC (sGC), cyclic GMP (cGMP), and protein kinase G (PKG), which was further proved to be the main protective mechanism in resisting ischemic injuries based on a variety of animal models, ranging from insects to mammals. [ 41–44 ] In our current study, we also found that both extracellular and intracellular NO productions were significantly increased with the APPJ treatment, which further contributed to a neuroprotective effect on the OGD‐injured cells. But further studies were still needed to reveal the molecular mechanisms.…”

Section: Resultssupporting

confidence: 65%

Atmospheric pressure plasma treatments protect neural cells from ischemic stroke‐relevant injuries by targeting mitochondria

Yan

Zhang

Ouyang

et al. 2020

Plasma Processes & Polymers

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Most studies regarding plasma biomedicine applications mainly focus on the oxidative and/or nitrative stress on bacteria, cancer cells, and other treatment objects. In this study, we evaluate the protective effect of appropriate atmospheric pressure plasma jet (APPJ) treatments on oxygen and glucose deprivation (OGD)-induced neural cell apoptosis, which is a major pathological process during ischemic stroke, based on the physiological functions of NO. Results show that APPJ treatment reduces the OGD-induced apoptosis by weakening typical OGD injury consequences including loss of mitochondrial membrane potential, the release of cytochrome c from the mitochondria into the cytoplasm, lower antiapoptotic Bcl-2 expression, and upregulating the proapoptotic protein Bax. Furthermore, APPJ increased intracellular NO production, which is closely related to the cytoprotective effect of APPJ.

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Section: Resultssupporting

confidence: 65%

Atmospheric pressure plasma treatments protect neural cells from ischemic stroke‐relevant injuries by targeting mitochondria

Yan

Zhang

Ouyang

et al. 2020

Plasma Processes & Polymers

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“…The cGMP-PKG signaling pathway could contribute to the attenuation of hyperlipidemia by Lei-gong-gen formula granules in rats, and this pathway has long been known to be a crucial therapeutic target in injury (Braun et al, 2018;Lan et al, 2020). As expected, we also discovered that a number of hypoxiarelated DEGs and metabolic pathways were significantly enriched in cGMP-PKG signaling pathway by analyzing the results of KEGG pathway enrichment, for example, adenosine 5′-phosphate (com_27274_pos), adenosine (com_190_pos) and MADS-box transcription enhancer factor 2C (MEF2C), that may provide the cellular protection and serve as a potential therapeutic target for protect cell against injury of hypoxia (Mahneva et al, 2019). Likewise, PPARγ antagonizes the hypoxia-induced activation of hepatic stellate cells by cross-mediating the PI3K/AKT and cGMP/PKG signaling pathways (Zhang et al, 2018a).…”

Section: Effects Of Hypoxia On Transcription Expression and Metabolite Formation In Atii Cellssupporting

confidence: 66%

Transcriptome and Metabolome Integration Provides New Insights Into the Regulatory Networks of Tibetan Pig Alveolar Type II Epithelial Cells in Response to Hypoxia

et al. 2022

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Tibetan pigs show a widespread distribution in plateau environments and exhibit striking physiological and phenotypic differences from others pigs for adaptation to hypoxic conditions. However, the regulation of mRNAs and metabolites as well as their functions in the alveolar type II epithelial (ATII) cells of Tibetan pigs remain undefined. Herein, we carried out integrated metabolomic and transcriptomic profiling of ATII cells between Tibetan pigs and Landrace pigs across environments with different oxygen levels to delineate their signature pathways. We observed that the differentially accumulated metabolites (DAMs) and differentially expressed genes (DEGs) profiles displayed marked synergy of hypoxia-related signature pathways in either Tibetan pigs or Landrace pigs. A total of 1,470 DEGs shared between normoxic (TN, ATII cells of Tibetan pigs were cultured under 21% O2; LN, ATII cells of Landrace pigs were cultured under 21% O2) and hypoxic (TL, ATII cells of Tibetan pigs were cultured under 2% O2; LL, ATII cells of Landrace pigs were cultured under 2% O2) groups and 240 DAMs were identified. Functional enrichment assessment indicated that the hypoxia-related genes and metabolites were primarily involved in glycolysis and aldosterone synthesis and secretion. We subsequently constructed an interaction network of mRNAs and metabolites related to hypoxia, such as guanosine-3′, 5′-cyclic monophosphate, Gly-Tyr, and phenylacetylglycine. These results indicated that mitogen-activated protein kinase (MAPK) signaling, aldosterone synthesis and secretion, and differences in the regulation of MCM and adenosine may play vital roles in the better adaptation of Tibetan pigs to hypoxic environments relative to Landrace pigs. This work provides a new perspective and enhances our understanding of mRNAs and metabolites that are activated in response to hypoxia in the ATII cells of Tibetan pigs.

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“…A large number of genes are enriched in the "vascular smooth cell contraction" pathway, which may make blood vessels more contractile and more able to regulate blood vessel thickness and distribution and blood flow velocity [32,33]. A large number of genes are enriched in the "cGMP-PKG signaling pathway," which improves adaptability to high altitudes but may also increase the possibility of cardiovascular disease [34,35]. These genes are related to the regulation of contractility and relaxation of smooth muscle cells and help regulate blood pressure and flow, ensuring blood supply.…”

Section: Discussionmentioning

confidence: 99%

Single‐cell transcriptomic survey of cell diversity and functional changes in yak hearts at different altitude

et al. 2023

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The yak (Bos grunniens) is a species adapted to the hypoxic environment in the plateau area. The heart is a hypoxia-sensitive organ involved in this adaptation. Herein, we used single-cell RNA-seq technology and clustering to determine the presence of 11 cell populations in the yak heart. We analyzed gene expression differences and expression patterns in each cell subpopulation at different altitudes. The cells related to altitude changes are mainly smooth muscle cells and vascular endothelial cells. Of the four transcription factors (TFs, MEF2B, FOXP4, ARID5A, and HES4) found in smooth muscle cells, only MEF2B was specifically expressed in vascular smooth muscle cells. Three key TFs (HNF1B, DMRTA1, and ARNTL2) were also found in the cardiomyocyte module. Compared with data extracted from low-altitude yak, we observed that the high altitude yak has enhanced contraction and relaxation of vascular smooth muscle cells and an increased metabolic level of cardiomyocytes. These may be strategies for the yak to adapt to high-altitude hypoxia environments.

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NO/cGMP/PKG activation protects Drosophila cells subjected to hypoxic stress

Cited by 9 publications

References 66 publications

Atmospheric pressure plasma treatments protect neural cells from ischemic stroke‐relevant injuries by targeting mitochondria

Atmospheric pressure plasma treatments protect neural cells from ischemic stroke‐relevant injuries by targeting mitochondria

Transcriptome and Metabolome Integration Provides New Insights Into the Regulatory Networks of Tibetan Pig Alveolar Type II Epithelial Cells in Response to Hypoxia

Single‐cell transcriptomic survey of cell diversity and functional changes in yak hearts at different altitude

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