Differential expression and tissue distribution of parkin isoforms during mouse development

Huynh, Duong P.; Dy, Maria; Nguyen, Dung; Kiehl, Tim-Rasmus; Pulst, Stefan M.

doi:10.1016/s0165-3806(01)00234-6

Cited by 37 publications

(21 citation statements)

References 25 publications

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“…Although none of these genes were previously reported to be expressed in islets, some of them are quite ubiquitous (c-Cbl and ␤-TRCP), while others are more tissue specific (parkin is mostly expressed in certain brain areas) (37). The polyubiquitin genes are rapidly activated in stress situations.…”

Section: Discussionmentioning

confidence: 96%

Evidence for a Role of the Ubiquitin-Proteasome Pathway in Pancreatic Islets

López-Avalos

Duvivier‐Kali

et al. 2006

Diabetes

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The ubiquitin-proteasome pathway is crucial for protein turnover. Part of the pathway involves deubiquitination, which is carried out by cystein proteases known as ubiquitin COOH-terminal hydrolases. The isoform Uch-L1 was found to be present in large amounts in rat islets by immunostaining, Western blot analysis, and RT-PCR. Culturing islets in high glucose concentrations (16.7 mmol/l) for 24 h led to decreased gene expression. Exposure to chronic hyperglycemia following 90% partial pancreatectomy also led to reduced Uch-L1 expression. Expression of other members of the ubiquitin-proteasome pathway studied after culturing islets at high glucose concentrations revealed little change except for modest declines in parkin, human ubiquitin-conjugating enzyme 5 (UbcH5), and ␤-TRCP (transducin repeat-containing protein). With the pancreatectomy model, expression of polyubiquitin-B and c-Cbl were increased and E6-associated protein was reduced. Further insight about the proteasome pathway was obtained with the proteasome inhibitor lactacystin, which in short-term 2-h experiments enhanced glucose-induced insulin secretion. An important role for the ubiquitinproteasome pathways in ␤-cells is suggested by the findings that changes in glucose concentration influence expression of genes in the pathway and that blockade of the proteasome degradation machinery enhances glucose-stimulated insulin secretion.

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Section: Discussionmentioning

confidence: 96%

Evidence for a Role of the Ubiquitin-Proteasome Pathway in Pancreatic Islets

López-Avalos

Duvivier‐Kali

et al. 2006

Diabetes

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“…␣-Synuclein is axonally transported and associates with vesicles in presynaptic terminals, suggesting a role in regulation of vesicle trafficking (148). Parkin is expressed primarily in neurons where it is localized at particularly high levels in neurites (137). Studies of the pathogenic actions of three missense mutations in ␣-synuclein (A53T, A30P, and G209A) have provided new insight into the events that lead to the dysfunction and degeneration of dopaminergic neurons in PD (Fig.…”

Section: B Genes That Cause or Increase Risk Of Neurodegenerative DImentioning

confidence: 99%

Modification of Brain Aging and Neurodegenerative Disorders by Genes, Diet, and Behavior

Mattson

Chan

Duan

2002

Physiological Reviews

400

249

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Multiple molecular, cellular, structural, and functional changes occur in the brain during aging. Neural cells may respond to these changes adaptively, or they may succumb to neurodegenerative cascades that result in disorders such as Alzheimer's and Parkinson's diseases. Multiple mechanisms are employed to maintain the integrity of nerve cell circuits and to facilitate responses to environmental demands and promote recovery of function after injury. The mechanisms include production of neurotrophic factors and cytokines, expression of various cell survival-promoting proteins (e.g., protein chaperones, antioxidant enzymes, Bcl-2 and inhibitor of apoptosis proteins), preservation of genomic integrity by telomerase and DNA repair proteins, and mobilization of neural stem cells to replace damaged neurons and glia. The aging process challenges such neuroprotective and neurorestorative mechanisms. Genetic and environmental factors superimposed upon the aging process can determine whether brain aging is successful or unsuccessful. Mutations in genes that cause inherited forms of Alzheimer's disease (amyloid precursor protein and presenilins), Parkinson's disease (α-synuclein and Parkin), and trinucleotide repeat disorders (huntingtin, androgen receptor, ataxin, and others) overwhelm endogenous neuroprotective mechanisms; other genes, such as those encoding apolipoprotein E4, have more subtle effects on brain aging. On the other hand, neuroprotective mechanisms can be bolstered by dietary (caloric restriction and folate and antioxidant supplementation) and behavioral (intellectual and physical activities) modifications. At the cellular and molecular levels, successful brain aging can be facilitated by activating a hormesis response in which neurons increase production of neurotrophic factors and stress proteins. Neural stem cells that reside in the adult brain are also responsive to environmental demands and appear capable of replacing lost or dysfunctional neurons and glial cells, perhaps even in the aging brain. The recent application of modern methods of molecular and cellular biology to the problem of brain aging is revealing a remarkable capacity within brain cells for adaptation to aging and resistance to disease.

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“…The amino acid sequence of the RING1 domain has a 57%, 56% and 56% identity as compared to that of human, mouse and rat, while the RING2 domain has a 56% identity when compared to that of human, mouse and rat. Such a high degree of conserved homology amongst these different species suggests that these domains are essential for Parkin functions, as previously mentioned by Huynh et al (2001). The RING-IBR-RING domain arrangement was predicted to regulate gene expression (Morett and Bork, 1999), but it is unlikely that Parkin has a function in the nucleus because Parkin is not localized in the nucleus (Kitada et al, 2000).…”

Section: R Esults and Discussionmentioning

confidence: 78%

“…A major transcript of 4.5 Kb was detected in a wide variety of human tissues (Kitada et al, 1998). Subsequent studies have demonstrated that parkin is expressed in certain neuronal cells of the central nervous system in vivo (Horowitz et al,1999;Huynh et al, 2001) and functions as a ubiquitin-protein ligase in vitro (Imai et al, 2000;Shimura et al, 2000), implying that Parkin suppresses neuronal cell degeneration by ubiquitinating misfolded proteins as an E3 enzyme. The expression of parkin in bovine peripheral nerve was investigated by RT-PCR and immunoblot analysis.…”

Section: Introductionmentioning

confidence: 99%