Translation of a unique transcript for protein isoaspartyl methyltransferase in haploid spermatids: Implications for protein storage and repair

Chavous, David A.; Hake, Laura E.; Lynch, Raymond; O’Connor, Clare M.

doi:10.1002/(sici)1098-2795(200006)56:2<139::aid-mrd3>3.0.co;2-0

Cited by 6 publications

(4 citation statements)

References 34 publications

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“…The effect of overexpressing CuZnSOD on lifespan was sex dependent, e.g., an increase in lifespan was observed in six of the strains of female drosophila, but only one strain of male drosophila showed an increase in lifespan [96]. The overexpression of MsrA has also been reported to increase the lifespan of Drosophila [97-99]. …”

Section: Discussionmentioning

confidence: 99%

Is the oxidative stress theory of aging dead?

Pérez¹,

Bokov²,

Remmen³

et al. 2009

Biochimica et Biophysica Acta (BBA) - General Subjects

532

412

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Currently, the Oxidative Stress (or Free Radical) Theory of Aging is the most popular explanation of how aging occurs at the molecular level. While data from studies in invertebrates (e.g., C. elegans and Drosophila) and rodents show a correlation between increased lifespan and resistance to oxidative stress (and in some cases reduced oxidative damage to macromolecules), direct evidence showing that alterations in oxidative damage/stress play a role in aging are limited to a few studies with transgenic Drosophila that overexpress antioxidant enzymes. Over the past eight years, our laboratory has conducted an exhaustive study on the effect of under- or overexpressing a large number and wide variety of genes coding for antioxidant enzymes. In this review, we present the survival data from these studies together. Because only one (the deletion of the Sod1 gene) of the 18 genetic manipulations we studied had an effect on lifespan, our data calls into serious question the hypothesis that alterations in oxidative damage/stress play a role in the longevity of mice.

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Section: Discussionmentioning

confidence: 99%

Is the oxidative stress theory of aging dead?

Pérez¹,

Bokov²,

Remmen³

et al. 2009

Biochimica et Biophysica Acta (BBA) - General Subjects

532

412

View full text Add to dashboard Cite

show abstract

“…In mammals, PIMT levels are notably higher in brain and testes than in other organs [72 -74], suggesting a particular importance for these tissues. Within the testes, particularly high levels of PIMT have been identified within spermatogenic cells, with an increase in both expression and activity correlated with progressive stages of spermatid development [75,76]. PIMT has been postulated to be important for repair of damaged proteins within mature spermatozoa, as these cells are translationally silent during epidymal storage [75,77].…”

Section: A Special Role For Pimt In the Brain And Testes?mentioning

confidence: 99%

Deamidation and isoaspartate formation in proteins: unwanted alterations or surreptitious signals?

Reissner

Aswad

2003

Cellular and Molecular Life Sciences (CMLS)

252

270

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Formation of betalinked Asp-Xaa peptide bonds--isoaspartyl (isoAsp) sites--arise in proteins via succinimide-linked deamidation of asparagine or dehydration of aspartate, reactions which represent a major source of spontaneous protein damage under physiological conditions. Accumulation of atypical isoaspartyl sites is minimized in vivo by the activity of protein L-isoaspartyl O-methyltransferase (PIMT), which regenerates a normal peptide bond. Loss of PIMT has harmful consequences, especially in neurons; thus, formation of isoAsp sites and their subsequent correction by PIMT is widely believed to constitute an important pathway of protein damage and repair. Recent evidence is mounting, however, that deamidation and isoaspartate formation may, in some instances, constitute a novel mechanism for intentional modification of protein structure. Herein we describe the mechanism of Asx rearrangement, summarize the evidence that PIMT serves an important repair function, and then focus on emerging evidence that deamidation and isoAsp formation may sometimes have a useful function.

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“…EEG analysis revealed that Pcmt1−/− mice display abnormal electrical activity approximately 50% of the time monitored, even when they are not overtly seizing [15]. Several other secondary phenotypes were also observed including reduced weight [16,30], sexual impotency or sterility [2,15] and kyphosis of the spine [12]. Treating Pcmt1−/− knockout mice with a combination of the antiepileptic drugs valproic acid and clonazepam restored normal growth and extended the life span, but to only about 80 days [15].…”

Section: Introductionmentioning

confidence: 99%

Improved rotorod performance and hyperactivity in mice deficient in a protein repair methyltransferase

Vitali¹,

Clarke²

2004

Behavioural Brain Research

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The protein l-isoaspartate (d-aspartate)-O-methyltransferase participates in the repair of age-induced protein damage by initiating the conversion of abnormal aspartyl residues within proteins to normal l-aspartyl residues. Previous studies have shown that mice deficient in the gene encoding this enzyme (Pcmt1−/−) accumulate damaged proteins, have altered levels of brain S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy), and suffer from epileptic seizures that result in death at an average age of about 42 days. In this study, we found that the behavior of Pcmt1−/− mice is abnormal in comparison to their wild-type (Pcmt1+/+) and heterozygous (Pcmt1+/−) littermates in two standard quantitative behavioral assays -the accelerating rotorod and the open-field test. On the accelerating rotorod, we found Pcmt1−/− mice actually perform significantly better than their heterozygous and wild-type littermates, a situation that has only been infrequently described in the literature and has not been described to date for epilepsy-prone mice. The Pcmt1−/− mice show, however, hyperactivity in the open-field test that becomes more pronounced with age, with a partial habituation with time in the chamber. Additionally, these mice demonstrate a strong thigmotaxic movement pattern. We present evidence that these phenotypes are not related to the alterations of the AdoMet/AdoHcy ratio in the brain and thus may be a function of the accumulation of damaged proteins. These results implicate a role for this enzyme in motor coordination and cerebellum development and suggest the importance of the function of the repair methyltransferase in hippocampal-dependent spatial learning.

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Translation of a unique transcript for protein isoaspartyl methyltransferase in haploid spermatids: Implications for protein storage and repair

Cited by 6 publications

References 34 publications

Is the oxidative stress theory of aging dead?

Is the oxidative stress theory of aging dead?

Deamidation and isoaspartate formation in proteins: unwanted alterations or surreptitious signals?

Improved rotorod performance and hyperactivity in mice deficient in a protein repair methyltransferase

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