Info on Glutathione

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> 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]