Early alterations of Gi/Go protein‐dependent transductional processes in the retina of diabetic animals

Abbracchio, Maria P.; Cattabeni, Flaminio; Giulio, Anna Maria Di; Finco, Cristina; Paoletti, Am; Tenconi, B.; Gorio, Alfredo

doi:10.1002/jnr.490290209

Cited by 12 publications

(11 citation statements)

References 22 publications

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“…The samples were boiled at 95°C for 4 min diabetes. The results of our studies have demonstrated that G protein-dependent transduction mechanisms are altered in diabetic animals; these functional defects develop earlier in the retina than in other central nervous system CNS areas (Abbracchio et al, 1989(Abbracchio et al, , 1991Finco et al, 1992). We have shown that in the striatum of 14-week alloxan-diabetic rats, there is a reduced efficacy of Gi/Go proteins in the modulation of dopamine-sensitive adenylate cyclase; at earlier stages of diabetes no changes were observed (Abbracchio et al, 1989).…”

Section: Assay For Mono-adp-ribosylationmentioning

confidence: 83%

“…The lack of insulin effects deserves further attention, but at this point the correlation between the modification of these other proteins and the establishment of diabetic neuropathy is unclear. It is well known that insulin treatment of diabetic rats prevents the onset of both neurological, neurochemical and functional peripheral nerve abnormalities (Di Giulio et al, 1995, in this issue) and the impairment of retina G protein-mediated signal transduction (Abbracchio et al, 1991). The results shown here indicate that insulin effects on retina membrane protein ADP-ribosylation are selective for a 39 K protein and there might be a correlation between this biochemical effect, the prevention of peripheral neuropathy and G protein dysfunction caused by diabetes mellitus.…”

Section: Adp-ribosylation In Diabetic Ratmentioning

confidence: 96%

“…G proteins in the retina are, however, more susceptible to diabetes. At 5 weeks after diabetes induction with alloxan, there is a marked attenuation of Gi-inhibitory activity, which is correlated by a reduced pertussis toxin-mediated incorporation of ADP-ribose (Abbracchio et al, 1991). Further studies have shown that, also in the striatum of 14-week alloxan-diabetic rats, the reduced inhibitory efficacy of Gi/Go proteins is correlated with a reduced pertussis toxin-mediated ADP-ribose incorporation (Finco et al, 1992).…”

Section: Assay For Mono-adp-ribosylationmentioning

confidence: 99%

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Nitric oxide‐sensitive protein ADP‐ribosylation is altered in rat diabetic neuropathy

Gorio

Donadoni

Giulio

1995

J of Neuroscience Research

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Endogenous ADP-ribosylation of proteins was studied in retina crude extract, membrane and cytosolic fractions of control and diabetic rats. ADP-ribosyltransferase activity is present in all cellular fractions, but protein ADP-ribosylation is reduced in diabetic rat retina. At least 6 proteins are labelled in the crude extract fraction and a similar number in the membrane preparation of control animals. In these preparations from diabetic retina, only two bands were labelled, the 85 K and 36 K for the crude extract, and the 97 K and 39 K for membranes. Labelling of 36 K and 39 K proteins was much less than in controls. In the cytosolic preparations of controls, two proteins of 85 K and 39 K are ADP-ribosylated, while in diabetic rat retina cytosol, only the 85 K is labelled. Treatment of diabetic rats with insulin normalized plasma glucose levels and prevented the alterations of the extent of ADP-ribosylation for the 38 K cytosolic, 39 K membrane and 36 K crude extracts proteins, but it failed to affect the other bands. These results suggest a hyperactivity of endogenous ADP-ribosylases in diabetic rat retina, so that the protein sites for ADP-ribosylation are no longer available. Since insulin treatment prevents the onset of neuropathy and of retinal G protein impairment (Abbracchio et al., J Neurosci Res 29:196-220, 1991) in diabetic rats and, in this study, normalizes ADP-ribosylation of 39 K, 38 K and 36 K proteins, we suggest that the abnormal endogenous ADP-ribosylation of these proteins might play a role in the onset of diabetic neuropathy.

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Section: Assay For Mono-adp-ribosylationmentioning

confidence: 83%

Section: Adp-ribosylation In Diabetic Ratmentioning

confidence: 96%

Section: Assay For Mono-adp-ribosylationmentioning

confidence: 99%

See 1 more Smart Citation

Nitric oxide‐sensitive protein ADP‐ribosylation is altered in rat diabetic neuropathy

Gorio

Donadoni

Giulio

1995

J of Neuroscience Research

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“…Diabetes‐induced changes in signaling through GPCRs could result from alterations in ligands presented to these receptors, but diabetes also is known to alter the expression of GPCRs, G proteins, and adenylate cyclase. Reduced expression of G i proteins has been reported in platelets, aorta, and retina from diabetic patients or rats (51–53). Expression of G qα and G i proteins was altered in aortas or aortic smooth muscle from diabetic rodents (54–56), the change apparently caused by reactive oxygen species.…”

Section: Discussionmentioning

confidence: 99%

Adrenergic and serotonin receptors affect retinal superoxide generation in diabetic mice: relationship to capillary degeneration and permeability

Du¹,

Cramer²,

Lee³

et al. 2015

FASEB j.

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Reactive oxygen species play an important role in the pathogenesis of diabetic retinopathy. We studied the role of adrenergic and serotonin receptors in the generation of superoxide by retina and 661W retinal cells in high glucose and of the α1-adrenergic receptor (AR) on vascular lesions of the retinopathy in experimentally diabetic C57Bl/6J mice (and controls) after 2 and 8 months. Compared with 5 mM glucose, incubating cells or retinal explants in 30 mM glucose induced superoxide generation. This response was reduced or ablated by pharmacologic inhibition of the α1-AR (a Gq-coupled receptor) or Gs-coupled serotonin (5-HT2, 5-HT4, 5-HT6, and 5-HT7) receptors or by activation of the Gi-coupled α2-AR. In elevated glucose, the α1-AR produced superoxide via phospholipase C, inositol triphosphate-induced Ca(2+) release, and NADPH oxidase, and pharmacologic inhibition of these reactions prevented the superoxide increase. Generation of retinal superoxide, expression of proinflammatory proteins, and degeneration of retinal capillaries in diabetes all were significantly inhibited with daily doxazosin or apocynin (inhibitors of α1-AR and NADPH oxidase, respectively), but increased vascular permeability was not significantly affected. Adrenergic receptors, and perhaps other GPCRs, represent novel targets for inhibiting the development of important features of diabetic retinopathy.

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“…Experimental diabetes was induced with a single subcutaneous injection of 100 mg/kg alloxan (Sigma Chemical Co., St. Louis, MO) dissolved in citrate-phosphate buffer at pH 4.5 (Di Giulio et al, 1988;Abbracchio et al, 1991). Three days after alloxan injection, we established the onset of diabetes by determining plasma glucose levels (GOP PAP test, Boehringer, Mannheim, Germany).…”

Section: Methodsmentioning

confidence: 99%

Progressive and selective changes in neurotrophic factor expression and substance p axonal transport induced by perinatal diabetes: Protective action of antioxidant treatment

Germani¹,

Lesma²,

Giulio³

et al. 1999

J. Neurosci. Res.

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Diabetes-induced embryo malformations and growth retardation are correlated with a variety of biochemical changes including oxidative stress. In this study, we show that the morphological alterations are correlated with progressive and selective changes of mRNA expression in specific neurotrophic factors. At embryological stage E-17, diabetes affected both embryo growth and NGF mRNA expression, which was reduced by as much as 90 and 56% in target tissues of sensory system such as tongue and intestine, respectively. The reduction in retina and heart was around 50%. Conversely, the mRNA expression of low-affinity neurotrophin receptor p75 was increased. At birth, BDNF mRNA expression was affected with a significant generalized reduction,while in vibrissae we observed a reduction of BDNF and p75 mRNAs and an increase of NGF. At postnatal day 14, pups from diabetic mothers showed reduced muscle levels of IGF-I, while we observed a partial impairment of substance P axonal transport at postnatal day 28. Treatment of diabetic mothers with silybin, a flavonoid with antioxidant properties, prevented most of the changes in neurotrophic factor expression and substance P axonal transport with no effects on hyperglycemia and embryo growth retardation. These results indicate that oxidative stress may influence neurotrophic factor synthesis in target territories during development. In addition, these data suggest that nervous system abnormalities observed in diabetic embryopathy may also derive by insufficient neurotrophic factor biosynthesis involving sequentially NGF in the embryo and BDNF and IGF-I in the early postnatal days. Insulin treatment of diabetic mothers normalized hyperglycemia and body growth, with consequent regular embryonic and postnatal development.

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Early alterations of Gi/Go protein‐dependent transductional processes in the retina of diabetic animals

Cited by 12 publications

References 22 publications

Nitric oxide‐sensitive protein ADP‐ribosylation is altered in rat diabetic neuropathy

Nitric oxide‐sensitive protein ADP‐ribosylation is altered in rat diabetic neuropathy

Adrenergic and serotonin receptors affect retinal superoxide generation in diabetic mice: relationship to capillary degeneration and permeability

Progressive and selective changes in neurotrophic factor expression and substance p axonal transport induced by perinatal diabetes: Protective action of antioxidant treatment

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