Trans-Plasma Membrane Electron Transport in Mammals: Functional Significance in Health and Disease

Principe, Domenico Del; Avigliano, Luciana; Savini, Isabella; Catani, Maria Valeria

doi:10.1089/ars.2010.3247

Cited by 49 publications

(36 citation statements)

References 316 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, this is an unusual function for a glycosylphosphatidylinositol-linked protein that is unlikely to utilize reducing equivalents from the cytosol because of linkage to the outer leaflet of the plasma membrane. It is likely that PrP C utilizes extracellular reducing agents for its FR activity such as conversion of ascorbate released from cells to dehydroascorbate through the intermediate ascorbyl free radical [32]. We believe that PrP C itself functions as a ferrireductase based on the following observations: 1) uptake of Fe 3+ is reduced in the liver and kidney of PrP −/− mice, organs involved in storage and reuptake of iron from the glomerular filtrate respectively and likely to express distinct set of proteins on the plasma membrane [this study; 22], and 2) exogenous expression of PrP C on HepG2 cells, proximal kidney tubule epithelial cells [this study; 22], neuroblastoma cells [19], and K562 cells, a hematopoietic cell line [unpublished observations] increases FR activity on the plasma membrane and in cell lysates, indicating a primary role of PrP C in iron uptake.…”

Section: Discussionmentioning

confidence: 99%

Prion protein functions as a ferrireductase partner for ZIP14 and DMT1

Tripathi

Haldar

Qian

et al. 2015

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Excess circulating iron is stored in the liver, and requires reduction of non-Tf-bound-iron (NTBI) and transferrin (Tf)-iron at the plasma membrane and endosomes respectively by ferrireductase (FR) proteins for transport across biological membranes through divalent metal transporters. Here, we report that prion-protein (PrPC), a ubiquitously expressed glycoprotein most abundant on neuronal cells, functions as a FR partner for divalent-metal transporter-1 (DMT1) and ZIP14. Thus, absence of PrPC in PrP-knock-out (PrP−/−) mice resulted in markedly reduced liver iron stores, a deficiency that was not corrected by chronic or acute administration of iron by the oral or intra-peritoneal routes. Likewise, preferential radiolabeling of circulating NTBI with 59Fe revealed significantly reduced uptake and storage of NTBI by the liver of PrP−/− mice relative to matched PrP+/+ controls. However, uptake, storage, and utilization of ferritin-bound iron that does not require reduction for uptake was increased in PrP−/− mice, indicating a compensatory response to the iron-deficiency. Expression of exogenous PrPC in HepG2-cells increased uptake and storage of ferric-iron (Fe3+), not ferrous-iron (Fe2+) from the medium, supporting the function of PrPC as a plasma membrane FR. Co-expression of PrPC with ZIP14 and DMT1 in HepG2 cells increased uptake of Fe3+ significantly, and surprisingly, increased the ratio of N-terminally truncated PrPC forms lacking the FR domain relative to full-length PrPC. Together, these observations indicate that PrPC promotes, and possibly regulates the uptake of NTBI through DMT1 and Zip14 via its FR activity. Implications of these observations for neuronal iron homeostasis under physiological and pathological conditions are discussed.

show abstract

Section: Discussionmentioning

confidence: 99%

Prion protein functions as a ferrireductase partner for ZIP14 and DMT1

Tripathi

Haldar

Qian

et al. 2015

Free Radical Biology and Medicine

View full text Add to dashboard Cite

show abstract

“…The ability of PALCAR treatment to reduce the appearance of herald I min observed in this study also lead us to propose that changes in the compositions of membrane phospholipid bilayers may alter the biophysical properties of MEP-associated currents in these cells. It also remains to be further investigated whether endogenous PALCAR or lysophosphatidylcholine [15,34] can be a substrate used to enhance MEP-elicited channels which indirectly activate the intrinsic pathway to apoptotic or necrotic changes by inducing changes in the mitochondrial permeability transition pores [2,3,35,36]. …”

Section: Discussionmentioning

confidence: 99%

Identification of Minuscule Inward Currents as Precursors to Membrane Electroporation-Induced Currents: Real-Time Prediction of Pore Appearance

Tsai

et al. 2013

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: The objective of this study is to examine the current signals in response to large hyperpolarizations with the aid of principal component analysis (PCA) to search for or even predict current fluctuations related to membrane electroporation-induced current (I_MEP). Methods: The characteristics of principal eigenvalues generated for I_MEP and the current signals at 10 sec prior to the start of initial I_MEP (I_Pre) were examined. As membrane hyperpolarizations were applied at 0.1 Hz, the appearance of I_MEP coincided with the higher principal eigenvalues extracted in PCA. Results: Subsequent addition of LaCl₃ (100 µM) greatly reduced I_MEP and associated principal eigenvalues. In real-time analysis for a single frame (i.e, 300 msec), in response to large hyperpolarization, multiple runs of heralded minuscule inward currents (I_min) occurring before large rise in current amplitudes were detected. With PCA, such heralded I_min was noted to coincide with the extreme principal eigenvalues. The duration of I_min together with large principal eigenvalues was influenced by different levels of membrane hyperpolarization. In GH3 cells, palmitoyl-L-carnitine (PALCAR), a long-chain acylcarnitine, effectively increased the I_MEP amplitude with an EC₅₀ value of 2.4 µM. However, in PALCAR-treated cells, the I_min together with higher principal eigenvalues disappeared, while in isoflurane-treated cells, I_min occurring before large rise of current amplitude remained intact. Similarly, the PCA analysis from I_Pre in RAW 264.6 macrophages showed the presence of herald I_min accompanied by the extreme principal eigenvalues. Conclusion: It is clear from this study that these large principal eigenvalues are representative of MEP-associated formation of electropores. Therefore, different compositions around the surface membrane of cells may alter the appearance of I_min followed by I_MEP emergence.

show abstract

“…With regard to membrane electron transport, the redox homeostasis of cells is deeply bound to the amount of NAD ? and NADH (Del Principe et al 2011;Gray et al 2011), which ratio is determined by movement of electrons from cellular NADH throughout plasma membrane to an external electron acceptor. In human trials, Herst and Berridge (2006) reported that a trans-membrane changes can act as signaling system capable to regulate the metabolism of host cells and it can change various cell functions such as cell redox homeostasis and protection against diseases.…”

Section: Discussionmentioning

confidence: 99%

Early trans-plasma membrane responses to Tobacco mosaic virus infection

et al. 2017

View full text Add to dashboard Cite

Early trans-plasma membrane behavior after in vivo mechanical inoculation of Nicotiana tabacum with Tobacco mosaic virus (TMV) was investigated and compared to virus quantification in leaf tissues. To identify early events related to virus/host interaction, the systemic virus TMV was used to infect lower leaves and tests were carried out on upper leaves which were not directly infected. Non-invasive microelectrodes were used to estimate trans-plasma membrane electron transport and membrane potential after artificial inoculum of virus, monitoring the plant for the following 15 days. Virus infection was assessed by ELISA and quantified by quantitative RT-PCR. Collected data showed that after 2-day post-inoculation (dpi), TMV was able to modify membrane parameters: transient hyperpolarization of trans-membrane potential was observed until 10 dpi, while redox activity in infected samples was higher compared to control until end of tests. Conversely, ELISA diagnostic test was not able to reveal the virus presence in tobacco leaves until 6 dpi, while leaf symptoms were manifested after 13 dpi.

show abstract

Trans-Plasma Membrane Electron Transport in Mammals: Functional Significance in Health and Disease

Cited by 49 publications

References 316 publications

Prion protein functions as a ferrireductase partner for ZIP14 and DMT1

Prion protein functions as a ferrireductase partner for ZIP14 and DMT1

Identification of Minuscule Inward Currents as Precursors to Membrane Electroporation-Induced Currents: Real-Time Prediction of Pore Appearance

Early trans-plasma membrane responses to Tobacco mosaic virus infection

Contact Info

Product

Resources

About