scholarly journals Flavored e-liquids increase cytoplasmic Ca2+ levels in airway epithelia

2020 ◽  
Vol 318 (2) ◽  
pp. L226-L241 ◽  
Author(s):  
Temperance R. Rowell ◽  
James E. Keating ◽  
Bryan T. Zorn ◽  
Gary L. Glish ◽  
Stephen B. Shears ◽  
...  
Keyword(s):  
Cell Growth ◽  
Biological Effects ◽  
Potential Toxicity ◽  
Airway Epithelia ◽  
Unknown Mechanism ◽  
Kinase C ◽  
Short And Long Term ◽  
Cellular Ca ◽  
Affect Cell Growth

E-cigarettes are noncombustible, electronic nicotine-delivery devices that aerosolize an e-liquid, i.e., nicotine, in a propylene glycol-vegetable glycerin vehicle that also contains flavors. While the effects of nicotine are relatively well understood, more information regarding the potential biological effects of the other e-liquid constituents is needed. This is a serious concern, because e-liquids are available in >7,000 distinct flavors. We previously demonstrated that many e-liquids affect cell growth/viability through an unknown mechanism. Since Ca2+ is a ubiquitous second messenger that regulates cell growth, we characterized the effects of e-liquids on cellular Ca2+ homeostasis. To better understand the extent of this effect, we screened e-liquids for their ability to alter cytosolic Ca2+ levels and found that 42 of 100 flavored e-liquids elicited a cellular Ca2+ response. Banana Pudding (BP) e-liquid, a representative e-liquid from this group, caused phospholipase C activation, endoplasmic reticulum (ER) Ca2+ release, store-operated Ca2+ entry (SOCE), and protein kinase C (PKCα) phosphorylation. However, longer exposures to BP e-liquid depleted ER Ca2+ stores and inhibited SOCE, suggesting that this e-liquid may alter Ca2+ homeostasis by short- and long-term mechanisms. Since dysregulation of Ca2+ signaling can cause chronic inflammation, ER stress, and abnormal cell growth, flavored e-cigarette products that can elicit cell Ca2+ responses should be further screened for potential toxicity.

scholarly journals Effects of Manganese Porphyrins on Cellular Sulfur Metabolism

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 980 ◽  
Author(s):  
Kenneth R. Olson ◽  
Yan Gao ◽  
Andrea K. Steiger ◽  
Michael D. Pluth ◽  
Charles R. Tessier ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Biological Effects ◽  
Sulfur Metabolism ◽  
Hek293 Cells ◽  
Redox Cycle ◽  
Major Site ◽  
Manganese Porphyrins ◽  
Short And Long Term ◽  
H2s Production

Manganese porphyrins (MnPs), MnTE-2-PyP5+, MnTnHex-2-PyP5+ and MnTnBuOE-2-PyP5+, are superoxide dismutase (SOD) mimetics and form a redox cycle between O2 and reductants, including ascorbic acid, ultimately producing hydrogen peroxide (H2O2). We previously found that MnPs oxidize hydrogen sulfide (H2S) to polysulfides (PS; H2Sn, n = 2–6) in buffer. Here, we examine the effects of MnPs for 24 h on H2S metabolism and PS production in HEK293, A549, HT29 and bone marrow derived stem cells (BMDSC) using H2S (AzMC, MeRho-AZ) and PS (SSP4) fluorophores. All MnPs decreased intracellular H2S production and increased intracellular PS. H2S metabolism and PS production were unaffected by cellular O2 (5% versus 21% O2), H2O2 or ascorbic acid. We observed with confocal microscopy that mitochondria are a major site of H2S production in HEK293 cells and that MnPs decrease mitochondrial H2S production and increase PS in what appeared to be nucleoli and cytosolic fibrillary elements. This supports a role for MnPs in the metabolism of H2S to PS, the latter serving as both short- and long-term antioxidants, and suggests that some of the biological effects of MnPs may be attributable to sulfur metabolism.

Down-regulation of protein kinase C and kinase inhibitors dissociate short- and long-term enhancement produced by one-trial conditioning of Hermissenda

1993 ◽  
Vol 69 (2) ◽  
pp. 636-641 ◽  
Author(s):  
T. Crow ◽  
J. Forrester
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Kinase Inhibitors ◽  
Protein Kinase Inhibitors ◽  
Cellular Plasticity ◽  
Short Term ◽  
Down Regulation ◽  
Kinase C ◽  
Short And Long Term

1. The visual system of Hermissenda has been studied extensively as a site of cellular plasticity produced by classical conditioning. Previous research has shown that one-trial conditioning, consisting of light paired with serotonin (5-HT) results in short- and long-term enhancement of light-elicited generator potentials in identified type B-photoreceptors. Recent evidence suggests that 5-HT exerts its effects on the induction of short-term enhancement by activation of protein kinase C (PKC), a Ca(2+)-activated and phospholipid-dependent protein kinase. However, the contribution of protein kinases in general, and specifically PKC in long-term enhancement has not been established. 2. The protein kinase inhibitors H-7 and sphingosine blocked the induction of short-term enhancement when applied before one-trial conditioning. However, the conditions that are sufficient to block the induction of short-term enhancement do not block long-term enhancement. Sphingosine and H-7 do not block the induction and expression of long-term enhancement when applied before one-trial conditioning. 3. Pretreatment before conditioning with 12-O-tetradecanoyl-phorbol-13-acetate (TPA), which leads to down-regulation of PKC, also did not block long-term enhancement. Down-regulation by itself did not produce enhancement, although the transient peak of light-elicited generator potentials was reduced by pretreatment with TPA. 4. The results suggest that the induction of short- and long-term enhancement involve parallel processes, and thus the expression of long-term cellular plasticity produced by one-trial conditioning does not depend on the induction or expression of short-term enhancement.

Recent updates on biomarkers of exposure and systemic toxicity in e-cigarette users and EVALI

2021 ◽  
Author(s):  
Samantha R McDonough ◽  
Irfan Rahman ◽  
Isaac Kirubakaran Sundar
Keyword(s):  
Potential Toxicity ◽  
Regulatory Decision ◽  
Research Areas ◽  
Epigenetic Biomarkers ◽  
Biomarkers Of Exposure ◽  
Drastic Increase ◽  
Novel Biomarkers ◽  
Short And Long Term ◽  
Traditional Tobacco

Electronic nicotine delivery systems (ENDS), or e-cigarettes, are emerging tobacco products that produce aerosols by heating e-liquids, which most often consist of propylene glycol and vegetable glycerin along with various flavoring compounds, bypassing the combustion that occurs in the use of traditional tobacco cigarettes. These products have seen a drastic increase in popularity in recent years both as smoking cessation devices as well as among younger generations, due in large part to the widespread perception among consumers that e-cigs are significantly less harmful for health than traditional tobacco cigarettes. Due to the novelty of ENDS as well as their rapidly increasing use, research into biomarkers of e-cig exposure and toxicity have lagged behind their popularity, leaving important questions about their potential toxicity unanswered. Research into potential biomarkers of acute, chronic e-cig use and E-cigarette- or Vaping-Associated Lung Injury is necessary for informing both clinical and regulatory decision-making. We aim to provide an updated review of recent research into potential circulating, genomic, transcriptomic and epigenetic biomarkers of exposure to and toxicity of e-cigs. We additionally highlight research areas that warrant additional study to gain better understanding of health risks associated with ENDS use, as well as to provide validation of existing data and methods for measuring and analyzing e-cig-associated biomarkers in human and animal biofluids, tissues and cells. This review also highlights ongoing efforts within the WNY Center for Research on Flavored Tobacco for research into novel biomarkers in extracellular vesicles that may be associated with short- and long-term ENDS use.

scholarly journals Role of Protein Kinase C (PKC) in Short- and Long-Term Cellular Responses

1988 ◽  
Vol 12 ◽  
pp. 73-79 ◽  
Author(s):  
Doriano Fabbro ◽  
Nachman Mazurek ◽  
Christoph Borner ◽  
Jean-François Conscience ◽  
Paul Erne
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cellular Responses ◽  
Kinase C ◽  
Short And Long Term

scholarly journals p53 Is Necessary for the Apoptotic Response Mediated by a Transient Increase of Ras Activity

2002 ◽  
Vol 22 (9) ◽  
pp. 2928-2938 ◽  
Author(s):  
Peihong Ma ◽  
Maureen Magut ◽  
XinBin Chen ◽  
Chang-Yan Chen
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Tumor Suppressor P53 ◽  
Wild Type ◽  
Apoptotic Response ◽  
Kinase C ◽  
The Status ◽  
Short And Long Term

ABSTRACT The tumor suppressor p53 eliminates cancer-prone cells via multiple mechanisms, including apoptosis. Ras elicits apoptosis in cells after protein kinase C (PKC) downregulation. However, the role of p53 in Ras-mediated apoptosis has not been fully investigated. Here, we demonstrate that mouse fibroblasts that express wild-type p53 are more susceptible to apoptosis elicited by PKC inhibition if Ras is transiently expressed or upregulated as opposed to stably expressed. In the latter case, p53 is frequently mutated. Transiently increased Ras activity induces Bax, and PKC inhibition augments this induction. Overexpression of E6 inactivates p53 and thereby suppresses both Bax induction and apoptosis. In contrast, Bax is not induced in stable ras transfectants, regardless of PKC inhibition. The data suggest that short- and long-term activation of Ras use a different mechanism(s) to initiate apoptosis. The status of p53 may contribute to such differences.

scholarly journals Preclinical assessment on neuronal regeneration in the injury-related microenvironment of graphene-based scaffolds

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Yun Qian ◽  
Xu Wang ◽  
Jialin Song ◽  
Wei Chen ◽  
Shuai Chen ◽  
...  
Keyword(s):  
Biological Effects ◽  
Axonal Outgrowth ◽  
Neuronal Regeneration ◽  
Nerve Injuries ◽  
Potential Toxicity ◽  
Regenerative Capacity ◽  
Function Recovery ◽  
Term Evaluation

AbstractAs the application of graphene nanomaterials gets increasingly attractive in the field of tissue engineering and regenerative medicine, the long-term evaluation is necessary and urgent as to their biocompatibility and regenerative capacity in different tissue injuries, such as nerve, bone, and heart. However, it still remains controversial about the potential biological effects of graphene on neuronal activity, especially after severe nerve injuries. In this study, we establish a lengthy peripheral nerve defect rat model and investigate the potential toxicity of layered graphene-loaded polycaprolactone scaffold after implantation during 18 months in vivo. In addition, we further identify possible biologically regenerative effects of this scaffold on myelination, axonal outgrowth, and locomotor function recovery. It is confirmed that graphene-based nanomaterials exert negligible toxicity and repair large nerve defects by dual regulation of Schwann cells and astroglia in the central and peripheral nervous systems. The findings enlighten the future of graphene nanomaterial as a key type of biomaterials for clinical translation in neuronal regeneration.

Role of Protein Kinase C (PKC) in Short- and Long-Term Cellular Responses

1988 ◽  
Vol 12 (Supplement) ◽  
pp. 73-79
Author(s):  
Doriano Fabbro ◽  
Nachman Mazurek ◽  
Christoph Borner ◽  
Jean-François Conscience ◽  
Paul Erne
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cellular Responses ◽  
Kinase C ◽  
Short And Long Term
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