Role of cysteine and glutathione in signal transduction, immunopathology and cachexia

Dröge, Wulf; Hack, Volker; Breitkreutz, Raoul; Holm, Eggert; Shubinsky, George; Schmid, Elmar; Galter, Dagmar

doi:10.1002/biof.5520080117

Cited by 48 publications

(24 citation statements)

References 23 publications

(47 reference statements)

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“…[36][37][38][39][40][41][42][43] Work with animal models also directly supports the idea that cancer-associated cachexia is driven by oxidative stress (ROS) and nitrosative stress (RNS) (a.k.a., a redox imbalance). [44][45][46] As such, stromal autophagy may be the requisite precursor of systemic cancer-associated cachexia.…”

Section: Anti-angiogenic Therapy Promotes Tumor Progression and Metasmentioning

confidence: 89%

The autophagic tumor stroma model of cancer or “battery-operated tumor growth”

et al. 2010

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The role of autophagy in tumorigenesis is controversial. Both autophagy inhibitors (chloroquine) and autophagy promoters (rapamycin) block tumorigenesis by unknown mechanism(s). This is called the "Autophagy Paradox". we have recently reported a simple solution to this paradox. we demonstrated that epithelial cancer cells use oxidative stress to induce autophagy in the tumor microenvironment. As a consequence, the autophagic tumor stroma generates recycled nutrients that can then be used as chemical building blocks by anabolic epithelial cancer cells. This model results in a net energy transfer from the tumor stroma to epithelial cancer cells (an energy imbalance), thereby promoting tumor growth. This net energy transfer is both unilateral and vectorial, from the tumor stroma to the epithelial cancer cells, representing a true host-parasite relationship. we have termed this new paradigm "The Autophagic Tumor Stroma Model of Cancer Cell Metabolism" or "Battery-Operated Tumor Growth." in this sense, autophagy in the tumor stroma serves as a "battery" to fuel tumor growth, progression and metastasis, independently of angiogenesis. Using this model, the systemic induction of autophagy will prevent epithelial cancer cells from using recycled nutrients, while the systemic inhibiton of autophagy will prevent stromal cells from producing recycled nutrients-both effectively "starving" cancer cells. we discuss the idea that tumor cells could become resistant to the systemic induction of autophagy by the upregulation of natural, endogenous autophagy inhibitors in cancer cells. Alternatively, tumor cells could also become resistant to the systemic induction of autophagy by the genetic silencing/deletion of pro-autophagic molecules, such as Beclin1. if autophagy resistance develops in cancer cells, then the systemic inhibition of autophagy would provide a therapeutic solution to this type of drug resistance, as it would still target autophagy in the tumor stroma. As such, an anti-cancer therapy that combines the alternating use of both autophagy promoters and autophagy inhibitors would be expected to prevent the onset of drug resistance. we also discuss why anti-angiogenic therapy has been found to promote tumor recurrence, progression and metastasis. More specifically, anti-angiogenic therapy would induce autophagy in the tumor stroma via the induction of stromal hypoxia, thereby converting a non-aggressive tumor type to a "lethal" aggressive tumor phenotype. Thus, uncoupling the metabolic parasitic relationship between cancer cells and an autophagic tumor stroma may hold great promise for anti-cancer therapy. Finally, we believe that autophagy in the tumor stroma is the local microscopic counterpart of systemic wasting (cancer-associated cachexia), which is associated with advanced and metastatic cancers. Cachexia in cancer patients is not due to decreased energy intake, but instead involves an increased basal metabolic rate and increased energy expenditures, resulting in a negative energy balance. importantly, when tumors...

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Section: Anti-angiogenic Therapy Promotes Tumor Progression and Metasmentioning

confidence: 89%

The autophagic tumor stroma model of cancer or “battery-operated tumor growth”

et al. 2010

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“…[26,27] Deficiency of cysteine leads to many diseases, such as slow growth, leucocyte loss, and liver, edema, muscle, and skin lesions. [28,29] The level of cysteine in vivo has been recognized as an important indicator for disease diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Photoelectrochemistry of Free‐Base‐Porphyrin‐Functionalized Zinc Oxide Nanoparticles and Their Applications in Biosensing

Lei

Wang

et al. 2011

Chemistry A European J

155

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The photoelectrochemical properties of free-base-porphyrin-functionalized zinc oxide nanoparticles were studied. A universal photoelectrochemical biosensing platform was constructed on indium tin oxide (ITO) by using the functional nanohybrid. The nanohybrid was synthesized by means of dentate binding of ZnO nanoparticles with carboxylic groups of 4,4',4'',4'''-(21H,23H-porphine-5,10,15,20-tetrayl)tetrakis(benzoic acid) (TCPP), and characterized with scanning electron microscopy, contact angle measurement, and spectral techniques. The nanohybrid-coated ITO electrode showed an efficient photocurrent response under irradiation at a wavelength of 360 nm, which could be greatly improved upon addition of cysteine by its oxidation at +0.3 V. The possible mechanism was that cysteine acts as a sacrificial electron donor to scavenge the photogenerated holes that locate on the excited state of TCPP, which then injects the photoexcitation electrons into the conduction band of ZnO nanoparticles, thereby transferring photoinduced electrons to the ITO electrode. Based on this enhanced photocurrent signal, a novel method for photoelectrochemical detection of cysteine was developed with a linear range of 0.6 to 157 μmol L(-1) in physiological media. The detection limit was 0.2 μmol L(-1) at a signal-to-noise ratio of 3. The novel strategy of cysteine analysis could provide an alternative method for monitoring biomolecules and extend the application of porphyrin-functionalized semiconductor nanoparticles.

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“…This design reflects the need of cysteine as an anchor group in polypeptide to stabilise metallic nanoparticles under different physiological conditions. L-cysteine (Cys) is an amino acid synthesised by the liver, and is involved in a variety of important cellular functions, including protein synthesis, detoxiEcation, and a metabolic process [9,10]. It is a small, zwitterionic molecule, and well used in biochemical and electrochemical research.…”

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confidence: 99%