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Gene Review

Uchl1  -  ubiquitin carboxyl-terminal esterase L1...

Rattus norvegicus

Synonyms: Neuron cytoplasmic protein 9.5, PGP 9.5, PGP9.5, UCH-L1, Ubiquitin carboxyl-terminal hydrolase isozyme L1, ...
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Disease relevance of Uchl1

  • The availability of the rat PGP9.5 clone provides a new approach to examine the function of PGP9.5 and the role that it plays in the pathology of neurodegenerative diseases [1].
  • Reinnervation after tibial fracture in the rat was studied by analyzing the occurrence of growth-associated protein 43 (GAP-43), a marker for regenerating nerve fibers, and protein gene product 9.5 (PGP-9.5), a marker for mature nerve fibers, by immunohistochemistry [2].
  • It may be concluded that radioiodinated MIBG is a reliable marker for the detection of cardiac adrenergic neuronal damage in doxorubicin-induced cardiomyopathy; it detects such damage earlier than do other clinical parameters and in this study showed a good correlation with the reduction in the neuronal population on PGP 9.5 stain [3].
  • We investigated whether UCH-L1 plays a neuroprotective role at the rostral ventrolateral medulla (RVLM), the origin of sympathetic neurogenic vasomotor tone in the medulla oblongata where the organophosphate insecticide mevinphos (Mev) acts to elicit cardiovascular toxicity [4].
  • After exposure to hypercapnic hypoxia for 3 months, the number of endocrine cells with PGP 9.5 and CGRP was markedly increased [5].

High impact information on Uchl1

  • Cysts (like the uterus) were robustly innervated, with many PGP9.5-stained neurites accompanying blood vessels and extending into nearby luminal epithelial layers [6].
  • Proteins encoded by two other genes in which mutations cause familial PD, parkin and UCH-L1, are involved in regulation of the ubiquitin-proteasome pathway, suggesting that dysregulation of the ubiquitin-proteasome pathway is involved in the mechanism by which these mutations cause PD [7].
  • METHODS: Neurones were counted in whole mount preparations of rat ileum stained immunohistochemically for the pan-neuronal marker PGP9.5, for choline acetyltransferase, or for nitric oxide synthase, or with NADH or NADPH histochemistry [8].
  • Cells immunoreactive for CGRP or for protein gene product 9.5 (PGP 9.5), a general marker of nerves and endocrine cells, were quantified in sections of lungs from hypoxic (21 days, 10 per cent O2) and normoxic rats [9].
  • Here we show that overexpression of UCH L1 potentiated ATP-induced currents due to the activation of P2X receptors that are widely distributed in the brain and involved in various biological activities including neurosecretion [10].

Biological context of Uchl1

  • To begin to assess the role of the Ub system in the axon, we studied expression and axonal transport of Ub and other stress proteins, as well as of Ub carboxyl-terminal hydrolase PGP 9.5, in the rat visual system in normal conditions and following heat-shock (HS) [11].
  • Intraepidermal innervation using PGP 9.5 immunostaining and plantar nerve histology were assessed at the end of the 12-week study [12].
  • Northern blot analyses showed no change in ubiquitin or PGP9.5 gene expression in hippocampus or cerebellum [13].
  • Lower lip innervation was investigated by detection of the general neuronal marker protein gene product 9.5 (PGP 9.5) and the growth-associated protein 43 (GAP-43), a neurochemical marker of neuronal plasticity [14].
  • During the morphogenesis, the PGP9.5 was expressed in the hair germ and hair peg elongated from the epidermis, and became restricted in the outer root sheath as the development progressed [15].

Anatomical context of Uchl1

  • The mRNA of PGP9.5 is most abundant in the rat brain and to a lesser degree in the testis [1].
  • In contrast to GAP-43, PGP-9.5-positive nerve fibers were observed only occasionally at 3 days postfracture but gradually increased in number from day 14 to 21 [2].
  • Postnatal development of periodontal ruffini endings in rat incisors: an immunoelectron microscopic study using protein gene product 9.5 (PGP 9.5) antibody [16].
  • 131I-MIBG uptake pattern was compared with histopathological results, the neuronal population on PGP 9.5 immunohistochemistry and the degree of myocyte damage assessed using a visual scoring system on haematoxylin and eosin and Masson's trichrome staining [3].
  • PGP 9.5-like immunofluorescence was also moderately expressed in apparent Schwann cells, in Merkel cells only in the external root sheath of vibrissal follicles, and in apparent dendritic and/or Langerhans cells usually located in the epidermis and occasionally in the follicles [17].

Associations of Uchl1 with chemical compounds


Other interactions of Uchl1


Analytical, diagnostic and therapeutic context of Uchl1

  • Western blotting using an anti-rat PGP9.5 antibody revealed the parallel distribution of mRNA and protein in various brain regions and testis [1].
  • Immunohistochemistry of the adult rat kidney for protein gene product 9.5 (PGP 9.5), a neuron-specific ubiquitin C-terminal hydrolase, demonstrated selective localization of the immunoreactivity in PEC [26].
  • RESULTS: PGP 9.5-positive neural structures were significantly reduced in grafts removed 1.5 and 3 months after transplantation compared with native kidneys with slightly increased numbers at 6 and 9 months after transplantation [19].
  • PGP 9.5-like immunofluorescence persisted in highly vacuolated profiles along the usual courses of medium to large-caliber axons 2 weeks after nerve transection [17].
  • RESULTS: In the nerve crush group, PGP9.5 positive nerves were decreased in number at 3 and 7 days, and then increased after 14 days in the muscle layer of the operated side [27].


  1. cDNA cloning and tissue distribution of a rat ubiquitin carboxyl-terminal hydrolase PGP9.5. Kajimoto, Y., Hashimoto, T., Shirai, Y., Nishino, N., Kuno, T., Tanaka, C. J. Biochem. (1992) [Pubmed]
  2. Bone reinnervation after fracture: a study in the rat. Li, J., Ahmad, T., Spetea, M., Ahmed, M., Kreicbergs, A. J. Bone Miner. Res. (2001) [Pubmed]
  3. Evaluation of cardiac adrenergic neuronal damage in rats with doxorubicin-induced cardiomyopathy using iodine-131 MIBG autoradiography and PGP 9.5 immunohistochemistry. Jeon, T.J., Lee, J.D., Ha, J.W., Yang, W.I., Cho, S.H. European journal of nuclear medicine. (2000) [Pubmed]
  4. De novo synthesis of ubiquitin carboxyl-terminal hydrolase isozyme l1 in rostral ventrolateral medulla is crucial to survival during mevinphos intoxication. Chang, C., Chang, A.Y., Chan, S.H. Shock (2004) [Pubmed]
  5. Laryngeal endocrine cells: topographic distribution and adaptation to chronic hypercapnic hypoxia. Yamamoto, Y., Kusakabe, T., Hayashida, Y., Yoshida, T., Matsuda, H., Atoji, Y., Suzuki, Y. Histochem. Cell Biol. (2000) [Pubmed]
  6. Innervation of ectopic endometrium in a rat model of endometriosis. Berkley, K.J., Dmitrieva, N., Curtis, K.S., Papka, R.E. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  7. Inducible expression of mutant alpha-synuclein decreases proteasome activity and increases sensitivity to mitochondria-dependent apoptosis. Tanaka, Y., Engelender, S., Igarashi, S., Rao, R.K., Wanner, T., Tanzi, R.E., Sawa, A., L Dawson, V., Dawson, T.M., Ross, C.A. Hum. Mol. Genet. (2001) [Pubmed]
  8. Restricted diet rescues rat enteric motor neurones from age related cell death. Cowen, T., Johnson, R.J., Soubeyre, V., Santer, R.M. Gut (2000) [Pubmed]
  9. Increased intracellular levels of calcitonin gene-related peptide-like immunoreactivity in pulmonary endocrine cells of hypoxic rats. Springall, D.R., Collina, G., Barer, G., Suggett, A.J., Bee, D., Polak, J.M. J. Pathol. (1988) [Pubmed]
  10. Potentiation of ATP-induced currents due to the activation of P2X receptors by ubiquitin carboxy-terminal hydrolase L1. Manago, Y., Kanahori, Y., Shimada, A., Sato, A., Amano, T., Sato-Sano, Y., Setsuie, R., Sakurai, M., Aoki, S., Wang, Y.L., Osaka, H., Wada, K., Noda, M. J. Neurochem. (2005) [Pubmed]
  11. Axonal transport of two major components of the ubiquitin system: free ubiquitin and ubiquitin carboxyl-terminal hydrolase PGP 9.5. Bizzi, A., Schaetzle, B., Patton, A., Gambetti, P., Autilio-Gambetti, L. Brain Res. (1991) [Pubmed]
  12. Tactile hyperesthesia, altered epidermal innervation and plantar nerve injury in the hindfeet of rats housed on wire grates. Mizisin, A.P., Kalichman, M.W., Garrett, R.S., Dines, K.C. Brain Res. (1998) [Pubmed]
  13. Ubiquitin, PGP 9.5 and dense body formation in trimethyltin intoxication: differential neuronal responses to chemically induced cell damage. Anderson, V.E., Hajimohammadreza, I., Gallo, J.M., Anderton, B.H., Uney, J., Brown, A.W., Nolan, C.C., Cavanagh, J.B., Leigh, P.N. Neuropathol. Appl. Neurobiol. (1992) [Pubmed]
  14. Immunocytochemical evidence of plasticity in the nervous structures of the rat lower lip. Verzé, L., Paraninfo, A., Ramieri, G., Viglietti-Panzica, C., Panzica, G.C. Cell Tissue Res. (1999) [Pubmed]
  15. Neuron-specific PGP9.5 expression in rat hair follicle development and cycle. Ohsawa, T. J. Dermatol. Sci. (2001) [Pubmed]
  16. Postnatal development of periodontal ruffini endings in rat incisors: an immunoelectron microscopic study using protein gene product 9.5 (PGP 9.5) antibody. Nakakura-Ohshima, K., Maeda, T., Ohshima, H., Noda, T., Takano, Y. J. Comp. Neurol. (1995) [Pubmed]
  17. The innervation of the mystacial pad of the rat as revealed by PGP 9.5 immunofluorescence. Rice, F.L., Kinnman, E., Aldskogius, H., Johansson, O., Arvidsson, J. J. Comp. Neurol. (1993) [Pubmed]
  18. Microarray analysis of gene expression in the rat vestibular nucleus complex following unilateral vestibular deafferentation. Horii, A., Masumura, C., Smith, P.F., Darlington, C.L., Kitahara, T., Uno, A., Mitani, K., Kubo, T. J. Neurochem. (2004) [Pubmed]
  19. Sympathetic reinnervation of rat kidney grafts. Grisk, O., Gröne, H.J., Rose, H.J., Rettig, R. Transplantation (2001) [Pubmed]
  20. Streptozotocin-induced diabetes in rats causes neuronal deficits in tyrosine hydroxylase and 5-hydroxytryptamine specific to mesenteric perivascular sympathetic nerves and without loss of nerve fibers. Webster, G.J., Petch, E.W., Cowen, T. Exp. Neurol. (1991) [Pubmed]
  21. Effect of NGF, BDNF, bFGF, aFGF and cell density on NPY expression in cultured rat dorsal root ganglion neurones. Kerekes, N., Landry, M., Lundmark, K., Hökfelt, T. J. Auton. Nerv. Syst. (2000) [Pubmed]
  22. Intestinal inflammation modulates expression of the synaptic vesicle protein neuronal calcium sensor-1. Lourenssen, S., Jeromin, A., Roder, J., Blennerhassett, M.G. Am. J. Physiol. Gastrointest. Liver Physiol. (2002) [Pubmed]
  23. Cortical expression of endothelin receptor subtypes A and B following middle cerebral artery occlusion in rats. Loo, L.S., Ng, Y.K., Zhu, Y.Z., Lee, H.S., Wong, P.T. Neuroscience (2002) [Pubmed]
  24. Growth-associated protein-43 immunohistochemical and ultrastructural changes in jaw muscle spindles of the rat following loss of occlusion. Santiwong, P., Muramoto, T., Soma, K., Takano, Y. Arch. Oral Biol. (2002) [Pubmed]
  25. Acrolein depletes the neuropeptides CGRP and substance P in sensory nerves in rat respiratory tract. Springall, D.R., Edginton, J.A., Price, P.N., Swanston, D.W., Noel, C., Bloom, S.R., Polak, J.M. Environ. Health Perspect. (1990) [Pubmed]
  26. Protein gene product 9.5 is selectively localized in parietal epithelial cells of Bowman's capsule in the rat kidney. Shirato, I., Asanuma, K., Takeda, Y., Hayashi, K., Tomino, Y. J. Am. Soc. Nephrol. (2000) [Pubmed]
  27. Increase of low-affinity neurotrophin receptor p75 and growth-associated protein-43 immunoreactivities in the rat urinary bladder during experimentally induced nerve regeneration. Wakabayashi, Y., Maeda, T., Aimi, Y., Kwok, Y.N. J. Urol. (1998) [Pubmed]
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