Info on Glutathione ---------- > From: Holly Moore > To: [log in to unmask] > Subject: glutathione stuff > Date: Thursday, March 20, 1997 10:01 AM > > Hi Jim > > Here are some references related to glutathione. I'll grab them at > the library. I'll make copies for you. > > Holly > > > <1> > Unique Identifier > 97041179 > Authors > Raha A. Tew KD. > Institution > Department of Pharmacology, Fox Chase Cancer Center, Philadelphia, PA 19111, > USA. > Title > Glutathione S-transferases. [Review] [363 refs] > Source > Cancer Treatment & Research. 87:83-122, 1996. > > <2> > Unique Identifier > 96386474 > Authors > Dekant W. > Institution > Institut fur Toxikologie und Pharmakologie, Universitat Wurzburg, Germany. > Title > Biosynthesis and cellular effects of toxic glutathione > S-conjugates. [Review] [115 refs] > Source > Advances in Experimental Medicine & Biology. 387:297-312, 1996. > > <3> > Unique Identifier > 97119162 > Authors > Jenner P. Olanow CW. > Institution > Neurodegenerative Diseases Research Centre, King's College London, UK. > Title > Oxidative stress and the pathogenesis of Parkinson's disease. [Review] [128 > refs] > Source > Neurology. 47(6 Suppl 3):S161-70, 1996 Dec. > Abstract > Current concepts of the pathogenesis of Parkinson's disease (PD) center on > the formation of reactive oxygen species and the onset of oxidative stress > leading to oxidative damage to substantia nigra pars compacta. Extensive > postmortem studies have provided evidence to support the involvement of > oxidative stress in the pathogenesis of PD; in particular, these include > alterations in brain iron content, impaired mitochondrial function, > alterations in the antioxidant protective systems (most notably superoxide > dismutase [SOD] and reduced glutathione [GSH]), and evidence > of oxidative damage to lipids, proteins, and DNA. Iron can > induce oxidative stress, and intranigral injections have been shown to induce > a model of progressive parkinsonism. A loss of GSH is associated with > incidental Lewy body disease and may represent the earliest biochemical > marker of nigral cell loss. GSH depletion alone may not result in damage to > nigral neurons but may increase susceptibility to subsequent toxic or free > radical exposure. The nature of the free radical species responsible for cell > death in PD remains unknown, but there is vidence of involvement of hydroxyl > radical (OH.), peroxynitrite, and nitric oxide. Indeed, OH. and peroxynitrite > formation may be critically dependent on nitric oxide formation. Central to > many of the processes involved in oxidative stress and oxidative damage in PD > are the actions of monoamine oxidase-B (MAO-B). MAO-B is essential for the > activation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to > 1-methyl-4-phenylpyridinium ion, for a component of the enzymatic conversion > of dopamine to hydrogen peroxide (H2O2), and for the activation of other > potential toxins such as isoquinolines and beta-carbolines. Thus, the > inhibition of MAO-B by drugs such as selegiline may protect against > activation of some toxins and free radicals formed from the MAO-B oxidation > of dopamine. In addition, selegiline may act through a mechanism unrelated to > MAO-B to increase neurotrophic factor activity and upregulate molecules such > as glutathione, SOD, catalase, and BCL-2 > protein, which protect against oxidant stress and apoptosis. > Consequently, selegiline may be advantageous in the long-term treatment of > PD. [References: 128] > > <4> > Unique Identifier > 97064389 > Authors > Bauer AJ. > Institution > Department of Medicine/Gastroenterology, University of Pittsburgh Medical > Center, PA 15261, USA. > Title > Transplantation-induced injuries of the intestinal muscularis and its > innervation: from preservation to chronic rejection. [Review] [11 refs] > Source > Transplantation Proceedings. 28(5):2539-41, 1996 Oct. > > <5> > Unique Identifier > 96400488 > Authors > Smith CV. Jones DP. Guenthner TM. Lash LH. Lauterburg BH. > Institution > Department of Pediatrics, Baylor College of Medicine, Houston 77030, USA. > Title > Compartmentation of glutathione: implications for the study > of toxicity and disease. [Review] [82 refs] > Source > Toxicology & Applied Pharmacology. 140(1):1-12, 1996 Sep. > Abstract > The fact that glutathione (GSH) plays many roles in > biological protective mechanisms and critical physiological functionshas > been recognized for decades. Conjugates, disulfides, and > other glutathione-derived products also have been studied as > biomarkers of the chemical natures or specific identities of key metabolites > of toxic agents and such studies have been crucial in the delineation of the > nature of the interactions of proximal toxicants with target biomolecules. > Despite the extensive evidence implicating the depletion and/or oxidation of > glutathione in a wide variety of human and experimental > toxicities, critical examination of such studies frequently reveals that > injury is not simply related to glutathione status. GSH is > compartmentalized at several levels and this compartmentation appears to > exert considerable influence on the relationships between > glutathione depletion or oxidation and the onset of injury. > Although compartmentation is usually viewed from the perspective of different > intracellular pools, the significance of extracellular > glutathione in functionally important pools is gaining > recognition. As the factors affecting the interactions of intracellular pools > with extracellular pools are delineated, studies in humans can be designed > and interpreted with greater precision and utility. [References: 82] > > <6> > Unique Identifier > 96318992 > Authors > Jenner P. > Institution > Biomedical Sciences Division, King's College London, UK. > Title > Oxidative stress in Parkinson's disease and other neurodegenerative > disorders. [Review] [51 refs] > Source > Pathologie Biologie. 44(1):57-64, 1996 Jan. > Abstract > The cause of cell death in neurodegenerative diseases remains unknown but the > formation of free radicals and the occurrence of oxidative stress may be a > common component of many, if not all, such disorders. For example, in > substantia nigra in Parkinson's diseases key alterations occur, in iron > handling, mitochondrial function and antioxidant defences, particularly > reduced glutathione. These indices of oxidative stress are > accompanied by evidence of free radical mediated damage inthe form of > increased lipid peroxidation and oxidation of DNA bases. The alterations in > oxidative stress occurring in Parkinson's disease appear not be related to > the administration of L-DOPA. Some alterations of oxidative stress are found > in other basal ganglia in degenerative disorders (multiple system atrophy, > progressive supranuclear palsy, Huntington's disease) but these have not been > investigated to the same extent. Similarly, examination of biochemical > changes occurring in Alzheimer's disease, motor neurone disease and diabetic > neuropathy also suggest the involvement of free radical mediated mechanisms > as a component of neurodegeneration. It is probable that irrespective of the > primary cause of individual neurodegenerative disorder, the onset of > oxidative stress is a common mechanism by which neuronal death occurs and > which contributes to disease progression. Clearly, therapeutic strategies > aimed at limiting free radical production and oxidative stress and/or damage > may slow the advance of neurodegenerative disease. [References: 51] > > <7> > Unique Identifier > 96260934 > Authors > Ebadi M. Srinivasan SK. Baxi MD. > Institution > Department of Pharmacology, University of Nebraska College of Medicine, Omaha > 68198-6260, USA. > Title > Oxidative stress and antioxidant therapy in Parkinson's disease. [Review] > [340 refs] > Source > Progress in Neurobiology. 48(1):1-19, 1996 Jan. > Abstract > Parkinson's disease, known also as striatal dopamine deficiency syndrome, is > a degenerative disorder of the central nervous system characterized by > akinesia, muscular rigidity, tremor at rest, and postural abnormalities. In > early stages of parkinsonism, there appears to be a compensatory increase in > the number of dopamine receptors to accommodate the initial loss of dopamine > neurons. As the disease progresses, the number of dopamine receptors > decreases, apparently due to the concomitant degeneration of dopamine target > sites on striatal neurons. The loss of dopaminergic neurons in Parkinso's > disease results in enhanced metabolism of dopamine, augmenting the formation > of H2O2, thus leading to generation of highly neurotoxic hydroxyl radicals > (OH.). The generation of free radicals can also be produced by > 6-hydroxydopamine or MPTP which destroys striatal dopaminergic neurons > causing parkinsonism in experimental animals as well as human beings. Studies > of the substantia nigra after death in Parkinson's disease have suggested the > presence of oxidative stress and depletion of reduced > glutathione; a high level of total iron with reduced level > of ferritin; and deficiency of mitochondrial complex I. New approaches > designed to attenuate the effects of oxidative stress and to provide > neuroprotection of striatal dopaminergic neurons in Parkinson's disease > include blocking dopamine transporter by mazindol, blocking NMDA receptors by > dizocilpine maleate, enhancing the survival of neurons by giving > brain-derived neurotrophic factors, providing antioxidants such as vitamin E, > or inhibiting monoamine oxidase B (MAO-B) by selegiline. Among all of these > experimental therapeutic refinements, the use of selegiline has been most > successful in that it has been shown that selegiline may have a neurotrophic > factor-like action rescuing striatal neurons and prolonging the survival of > patients with Parkinson's disease. [References: 340] > > <8> > Unique Identifier > 96296549 > Authors > O'Brien ML. Tew KD. > Institution > Department of Pharmacology, University of Pennsylvania, Philadelphia 19111, > USA. > Title > Glutathione and related enzymes in multidrug resistance. > [Review] [147 refs] > Source > European Journal of Cancer. 32A(6):967-78, 1996 Jun. > > <9> > Unique Identifier > 96279694 > Authors > Duggin GG. > Institution > Department of Renal Medicine, Royal Prince Alfred Hospital, Sydney, > Australia. > Title > Combination analgesic-induced kidney disease: the Australian experience. > [Review] [41 refs] > Source > American Journal of Kidney Diseases. 28(1 Suppl 1):S39-47, 1996 Jul. > Abstract > Analgesi nephropathy is a unique drug-induced kidney disease characterized > pathologically by renal papillary necrosis and chronic interstitial > nephritis, and is the result of excessive consumption of combination > antipyretic analgesics. The clinical features of the disorder relate mainly > to the papillary necrosis, renal colic, and obstructive uropathy and the > development of chronic renal failure in a small percentage of patients. There > are significant geographic variations in the clinical features that may be > related to the differing combinations of analgesics. The pathogenesis of the > disease is in part related to the kidneys' ability to concentrate drugs in > the papillae. The following sequence of events presents a plausible > explanation for the evolution of the disease. If a combination of phenacetin > and aspirin is ingested, the following steps occur. Phenacetin is converted > in the gut and liver to acetaminophen by first-pass metabolism. Acetaminophen > is then taken up by the kidney and excreted. During its excretion, > acetaminophen becomes concentrated in the papillae of the kidney during > physiologic degrees of antidiuresis, the concentration being up to five times > the intracellular concentration of other tissues. Acetaminophen undergoes > oxidative metabolism by prostaglandin H synthase to a reactive quinoneimine > that is conjugated to glutathione. If acetaminophen is > present alone, there is sufficient glutathione generated in > the papillae to detoxify the reactive intermediate. If the acetaminophen is > ingested with aspirin, the aspirin is converted to salicylate and salicylate > becomes highly concentrated in both the cortex and papillae of the kidney. > Salicylate is a potent depletor of glutathione. The > mechanism is not completely understood; however, the inhibition of the > production of NADPH via the pentose shunt is a possible explanation. With the > cellular glutathione depleted, the reactive metabolite of > acetaminophen then produces lipid peroxides and arylation of tissue proteins, ultimately resulting in necrosis of the papillae. > [References: 41] > > <10> > Unique Identifier > 96218587 > Authors > Taylor CG. Nagy LE. Bray TM. > Institution > Department of Foods and Nutrition, University of Manitoba, Winnipeg, Canada. > Title > Nutritional and hormonal regulation of glutathione > homeostasis. [Review] [129 refs] > Source > Current Topics in Cellular Regulation. 34:189-208, 1996. > > <11> > Unique Identifier > 96094704 > Authors > Meydani SN. Wu D. Santos MS. Hayek MG. > Institution > Nutritional Immunology Laboratory, Jean Mayer US Department of Agriculture > Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, > USA. > Title > Antioxidants and immune response in aged persons: overview of present > evidence. [Review] [146 refs] > Source > American Journal of Clinical Nutrition. 62(6 Suppl):1462S-1476S, 1995 Dec. > Abstract > The oxidant-antioxidant balance is an important determinant of immune cell > function, including maintaining the integrity and functionality of membrane > lipids, cellular proteins, and nucleic acids and controlling > signal transduction and gene expression in immune cells. Optimal amounts of > antioxidants are needed for maintenance of the immune response across all age > groups. This need might be more critical, however, in aged persons. > Age-associated dysregulation of immune response, particularly of T > cell-mediated function, is well documented. The well-known age-related > increase in free radical formation and lipid peroxidation contributes, at > least in part, to this phenomenon. We summarize animal and human studies > undertaken by ourselves as well as other investigators on the effects of > antioxidants, vitamin E, beta-carotene, and glutathione on > the immune response of aged persons. The underlying mechanisms for the > antioxidant nutrients' effects as well as their health implications for aged > persons are discussed. [References: 146] > > <12> > Unique Identifier > 96275338 > Authors > Schulz JB. Matthews RT. Beal MF. > Institution > Neurochmistry Laboratory, Massachusetts General Hospital, Boston, USA. > Title > Role of nitric oxide in neurodegenerative diseases. [Review] [42 refs] > Source > Current Opinion in Neurology. 8(6):480-6, 1995 Dec. > Abstract > Besides its role as a mediator of several physiological functions, nitric > oxide appears to be a neurotoxin under conditions of excessive production, > which suggests a role for nitric oxide in neurodegenerative diseases. An > increasing body of evidence has implicated excitotoxicity as a mechanism of > cell death in both acute and chronic neurologic diseases. Activation of > excitatory amino acid receptors leads to activation of neuronal nitric oxide > synthase by an increase in intracellular calcium concentrations. Nitric oxide > may inhibit key enzymes of energy metabolism, damage DNA, deplete > intracellular glutathione, and react with superoxide to form > peroxynitrite. The latter is a highly reactive molecule, a potent oxidizing > agent known to initiate lipid peroxidation, hydroxylation and nitration of > aromatic amino acid residues, and sulfhydryl oxidation of > proteins, and to decompose to nitrogen dioxide and species > with hydroxyl-like reactivity. There now is evidence that the neuronal > production of nitric oxide and the formation of peroxynitrite occurs in vivo. > [References: 42]