Exosomes Are Involved in Mediating Radiation Induced Bystander Signaling in Human Keratinocyte Cells

Jella, Kishore Kumar; Rani, Sweta; O’Driscoll, Lorraine; McClean, Brendan; Byrne, Hugh J.; Lyng, Fiona M.

doi:10.1667/rr13337.1

Cited by 153 publications

(89 citation statements)

References 53 publications

(57 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Exosomes were isolated as described by Jella et al [34] with the following modifications. Conditioned media from cell monolayers was collected every 48 hours from the inside (apical) or outside (basolateral) compartments while the cells were grown on permeable transwell inserts.…”

Section: Methodsmentioning

confidence: 99%

Exosomal GAPDH from Proximal Tubule Cells Regulate ENaC Activity

Jella

Yue

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

Exosomes are nanometer-scale, cell-derived vesicles that contain various molecules including nucleic acids, proteins, and lipids. These vesicles can release their cargo into adjacent or distant cells and mediate intercellular communication and cellular function. Here we examined the regulation of epithelial sodium channels in mpkCCD cells and distal tubule Xenopus 2F3 cells by exosomes isolated from proximal tubule LLC-PK1 cells. Cultured mpkCCD cells were stained with CTX coupled to a green fluorophore in order to label the cell membranes and freshly isolated exosomes from LLC-PK1 cells were labeled with the red lipophilic dye PKH26 in order to visualize uptake of exosomes into the cells. Single-channel patch clamp recordings showed the open probability of ENaC in Xenopus 2F3 cells and in freshly isolated split-open tubules decreased in response to exogenous application of exosomes derived from LLC-PK1 proximal tubule cells. Active GAPDH was identified within exosomes derived from proximal tubule LLC-PK1 cells. The effect on ENaC activity in Xenopus 2F3 cells was blunted after application of exosomes transfected with the GAPDH inhibitor heptelidic acid. Also, we show GAPDH and ENaC subunits associate in mpkCCD cells. These studies examine a potential role for exosomes in the regulation of ENaC activity and examine a possible mechanism for communication from proximal tubule cells to distal tubule and collecting duct cells.

show abstract

Section: Methodsmentioning

confidence: 99%

Exosomal GAPDH from Proximal Tubule Cells Regulate ENaC Activity

Jella

Yue

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…The data represent AM ± SEM of three independent experiments. *p \ 0.05 compared to the pertinent control group oxygen species or cytokines and also by the release of microvesicles (Klammer et al 2015;Hei et al 2008;Kumar Jella et al 2014;Al-Mayah et al 2012). Furthermore, the importance of extracellular microvesicles in cancer treatment is gaining recognition as there is emerging evidence of their role in intercellular communication through which they influence the functioning of the nontargeted cells (El-Andaloussi et al 2013).…”

Section: Discussionmentioning

confidence: 96%

“…However, in the B16F1 cell line, the formation of microvesicles did not increase after irradiation, which indicates that in this line, the bystander effect is mediated by mechanisms other than microvesicle shedding. Since in our and in other studies increased microvesicle formation has been observed after cell irradiation in some of the cell lines (Al-Mayah et al 2012;Kumar Jella et al 2014), we decided to use this parameter to further evaluate the bystander effect after electroporation.…”

Section: Discussionmentioning

confidence: 99%

“…The damage in the unirradiated cells consists of telomere aberrations, DNA damage and cell death (Hall and Giaccia 2006). Signals which cause damage of the neighboring cells can be released either through gap junctions (Azzam et al 1998) or as extracellular soluble substrates (Mothersill and Seymour 1998) and may be in the form of soluble substrates, such as reactive oxygen species (Klammer et al 2015) and cytokines (Hei et al 2008), or they may travel to the bystander cells via microvesicles (Kumar Jella et al 2014). Microvesicles are extracellular fragments of cell membrane containing different proteins, RNA molecules and other agents, which can influence various signaling pathways in the target cells, including pathways leading to oncogenesis, cell death or activation of the immune response (Al-Mayah et al 2012;Kumar Jella et al 2014).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Bystander Effect Induced by Electroporation is Possibly Mediated by Microvesicles and Dependent on Pulse Amplitude, Repetition Frequency and Cell Type

et al. 2016

View full text Add to dashboard Cite

Bystander effect, a known phenomenon in radiation biology, where irradiated cells release signals which cause damage to nearby, unirradiated cells, has not been explored in electroporated cells yet. Therefore, our aim was to determine whether bystander effect is present in electroporated melanoma cells in vitro, by determining viability of non-electroporated cells exposed to medium from electroporated cells and by the release of microvesicles as potential indicators of the bystander effect. Here, we demonstrated that electroporation of cells induces bystander effect: Cells exposed to electric pulses mediated their damage to the non-electroporated cells, thus decreasing cell viability. We have shown that shedding microvesicles may be one of the ways used by the cells to mediate the death signals to the neighboring cells. The murine melanoma B16F1 cell line was found to be more electrosensitive and thus more prone to bystander effect than the canine melanoma CMeC-1 cell line. In B16F1 cell line, bystander effect was present above the level of electropermeabilization of the cells, with the threshold at 800 V/cm. Furthermore, with increasing electric field intensities and the number of pulses, the bystander effect also increased. In conclusion, electroporation can induce bystander effect which may be mediated by microvesicles, and depends on pulse amplitude, repetition frequency and cell type.

show abstract

“…Furthermore, EVs are found to play key roles when studied in relation to physiology, oncology as well as immunology [8] [9] [10] [11] [12]. When EV morphology is studied with cryo-electron microscopy (cryo-EM), most vesicles are round, but they can also have multiple other shapes [13] [14] [15] [16] [17].…”

Section: Introductionmentioning

confidence: 99%