Volume Regulation in Transporting Epithelia

Graf, J.; Guggino, William B.; Turnheim, Klaus

doi:10.1007/978-3-642-77124-8_3

Cited by 7 publications

(10 citation statements)

References 241 publications

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“…Myo- inositol normalized to unsuppressed water is susceptible to bias introduced by edema, which may accompany substance dependence and/or neuroinflammation [44, 58, 59]. As stated above, myo- inositol is involved in cell volume regulation, and thus, may be directly influenced by edema and/or osmotic changes [36, 43-47, 54-56]. Further, as described below, normalization to NAA may be susceptible to bias due to neurodegeneration [60], which may or may not be attributed to chronic neuroinflammation [35].…”

Section: Using Imaging To Measure Neuroimmune Biomarkersmentioning

confidence: 99%

“…Clinical studies have reported elevated myo- inositol levels in conditions not known to be associated with inflammation (reviewed in [53]). Also, myo- inositol is sensitive to osmotic changes [54-56] and edema [36, 43-47] which may confound neuroimmune investigations in SUDs (e.g., alcohol is known to exert osmotic effects [57]). Thus, myo- inositol is thought to be sensitive to neuroimmune signaling but exhibits only modest specificity.…”

Section: Using Imaging To Measure Neuroimmune Biomarkersmentioning

confidence: 99%

“…Myo- inositol is a putative glial marker located in cultured astrocytes [36-39] and is associated with microglia [40]. Myo- inositol functions as a secondary messenger [41, 42], osmolyte [36, 43-47], and precursor of membrane phospholipids [42]. Myo- inositol is synthesized from glucose and can be produced in significant quantities within minutes [48].…”

Section: Using Imaging To Measure Neuroimmune Biomarkersmentioning

confidence: 99%

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Imaging Biomarkers of the Neuroimmune System among Substance Use Disorders: A Systematic Review

et al. 2019

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There is tremendous interest in the role of the neuroimmune system and inflammatory processes in substance use disorders (SUDs). Imaging biomarkers of the neuroimmune system in vivo provide a vital translational bridge between preclinical and clinical research. Herein, we examine two imaging techniques that measure putative indices of the neuroimmune system and review their application among SUDs. Positron emission tomography (PET) imaging of 18 kDa translocator protein availability is a marker associated with microglia. Proton magnetic resonance spectroscopy quantification of myo-inositol levels is a putative glial marker found in astrocytes. Neuroinflammatory responses are initiated and maintained by microglia and astrocytes, and thus represent important imaging markers. The goal of this review is to summarize neuroimaging findings from the substance use literature that report data using these markers and discuss possible mechanisms of action. The extant literature indicates abused substances exert diverse and complex neuroimmune effects. Moreover, drug effects may change across addiction stages, i.e. the neuroimmune effects of acute drug administration may differ from chronic use. This burgeoning field has considerable potential to improve our understanding and treatment of SUDs. Future research is needed to determine how targeting the neuroimmune system may improve treatment outcomes.

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Section: Using Imaging To Measure Neuroimmune Biomarkersmentioning

confidence: 99%

Section: Using Imaging To Measure Neuroimmune Biomarkersmentioning

confidence: 99%

Section: Using Imaging To Measure Neuroimmune Biomarkersmentioning

confidence: 99%

See 1 more Smart Citation

Imaging Biomarkers of the Neuroimmune System among Substance Use Disorders: A Systematic Review

et al. 2019

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“…et al, 1988] and a collection of papers dealing with the interaction of cell volume and cell function | Bianchini and Grinstein. 1992;Graf et al. 1992: Halestrap.…”

Section: Introductionmentioning

confidence: 99%

The Biological Significance of Cell Volume

Läng

Ritter²,

Völkl³

et al. 1993

Kidney Blood Press Res

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To survive, cells have to avoid excessive alterations of their volume. To this end, cells have developed a complex machinery of cell volume regulatory mechanisms comprising transport across the cell membrane and metabolism. Upon cell swelling, they loose electrolytes mainly via selective K⁺ channels and unselective ion channels and/or KCl symport, upon cell shrinkage they accumulate ions by Na⁺, K⁺,2Cl^- cotransport and parallel operation of Na⁺/H⁺ exchange and Cl^-/ HC0₃^- exchange. In addition, cell shrinkage stimulates glycogenolysis, proteolysis and formation of organic osmolytes such as amino acids, methylamines and polyols. Cell swelling stimulates formation of glycogen and proteins and cellular release of organic osmolytes. Alterations of cell volume do play a crucial role in the regulation of cell function, as illustrated by four examples: 1. Epithelial transport may lead to cell swelling, which then triggers volume regulatory mechanisms modifying transcellular transport.2. Insulin swells hepatocytes by activation of Na⁺, K⁺,2Cl^- cotransport and Na⁺/H⁺ exchange, glucagon shrinks those cells by activation of ion channels. The respective volume changes participate in the regulation of cellular protein and glycogen metabolism by these hormones.3. Growth factors and expression of ras oncogene activate Na⁺ , K⁺ ,2Cl^- cotransport and Na⁺/H⁺ exchange leading to the respective cell swelling.4. Hepatocyte swelling triggers a hepatorenal reflex decreasing renal blood flow.

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“…Both hyper‐ and hypotonic conditions alter the cellular hydration state affecting cell morphology and protein function. The renal medulla is the prototypical tissue which is routinely exposed to high levels of NaCl caused by antidiuresis and diuresis and therefore the cells are permanently stressed by osmotic forces (1–3).…”

Section: Introductionmentioning

confidence: 99%

Lipophilic prodrugs of amino acids and vitamin E as osmolytes for the compensation of hyperosmotic stress in human keratinocytes

Graf¹,

Kock²,

Böck³

et al. 2009

Experimental Dermatology

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Skin keratinocytes are subjected to changing osmotic conditions and evolved counteracting mechanisms. Particularly, the expression of osmolyte transporters serves for the maintenance of cell volume in a hypertonic environment. In this study, we show that hyperosmotic stress significantly decreases the proliferation in HaCaT keratinocytes. Supplementation of the culture medium with the amino acids glycine, sarcosine, betaine, taurine and proline restored the proliferation indicating osmoprotective properties of these substances. Amino acids are highly polar molecules and therefore unable to penetrate into deeper epidermal layers after topical application. Thus, we utilized a prodrug concept in which the tested amino acids are coupled to a lipophilic moiety. Ethyl glycinate as a first model compound also showed an osmoprotective effect. In addition, improved penetration of the glycine derivative into deeper epidermal layers could be demonstrated. The prodrug concept was further developed by using the lipid soluble antioxidant alpha-tocopherol as a lipophilic moiety. The derivatives d,l-alpha-tocopheryl-(mono-) glycinate (TMG) and d,l-alpha-tocopheryl-(mono-) prolinate caused an increase in proliferation of HaCaT keratinocytes under salt stress and a decrease in apoptosis induced by hypertonic conditions. Furthermore, the osmoprotective effect of d,l-TMG could be corroborated in normal human keratinocytes. Therefore, it seems feasible that amino acids and their lipophilic derivatives may help to improve the osmotic balance and the hydration of skin. Clinical and cosmetic indications such as atopic eczema, UV exposed skin or aged skin may benefit from this new concept.

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Volume Regulation in Transporting Epithelia

Cited by 7 publications

References 241 publications

Imaging Biomarkers of the Neuroimmune System among Substance Use Disorders: A Systematic Review

Imaging Biomarkers of the Neuroimmune System among Substance Use Disorders: A Systematic Review

The Biological Significance of Cell Volume

Lipophilic prodrugs of amino acids and vitamin E as osmolytes for the compensation of hyperosmotic stress in human keratinocytes

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