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Functional expression of carnitine/organic cation transporter OCTN1 in mouse brain neurons: possible involvement in neuronal differentiation.
Neurochem Int. 2012 Dec; 61(7):1121-32.NI

Abstract

The aim of the present study is to clarify the functional expression and physiological role in brain neurons of carnitine/organic cation transporter OCTN1/SLC22A4, which accepts the naturally occurring antioxidant ergothioneine (ERGO) as a substrate in vivo. After intracerebroventricular administration, the distribution of [(3)H]ERGO in several brain regions of octn1(-/-) mice was much lower than that in wild-type mice, whereas extracellular marker [(14)C]mannitol exhibited similar distribution in the two strains. The [(3)H]ERGO distribution in wild-type mice was well correlated with the amount of ERGO derived from food intake and the OCTN1 mRNA level in each brain region. Immunohistochemical analysis revealed colocalization of OCTN1 with neuronal cell markers microtubule-associated protein 2 (MAP2) and βIII-tubulin in mouse brain and primary cultured cortical neurons, respectively. Moreover, cultured cortical neurons exhibited time-dependent and saturable uptake of [(3)H]ERGO. These results demonstrate that OCTN1 is functionally expressed in brain neurons. The addition of ERGO simultaneously with serum to culture medium of cortical neurons attenuated mRNA and protein expressions of MAP2, βIII-tubulin and synapse formation marker synapsin I, and induced those of sex determining region Y-box 2 (Sox2), which is required to maintain the properties of undifferentiated neural stem cells. In neuronal model Neuro2a cells, knockdown of OCTN1 by siRNA reduced the uptake of [(3)H]ERGO with concomitant up-regulation of oxidative stress marker HO-1 and Sox2, and down-regulation of neurite outgrowth marker GAP43. Interestingly, the siRNA knockdown decreased the number of differentiated Neuro2a cells showing long neurites, but increased the total number of cells. Thus, OCTN1 is involved in cellular differentiation, but inhibits their proliferation, possibly via the regulation of cellular oxidative stress. This is the first evidence that OCTN1 plays a role in neuronal differentiation and proliferation, which are required for brain development.

Authors+Show Affiliations

Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22944603

Citation

Nakamichi, Noritaka, et al. "Functional Expression of Carnitine/organic Cation Transporter OCTN1 in Mouse Brain Neurons: Possible Involvement in Neuronal Differentiation." Neurochemistry International, vol. 61, no. 7, 2012, pp. 1121-32.
Nakamichi N, Taguchi T, Hosotani H, et al. Functional expression of carnitine/organic cation transporter OCTN1 in mouse brain neurons: possible involvement in neuronal differentiation. Neurochem Int. 2012;61(7):1121-32.
Nakamichi, N., Taguchi, T., Hosotani, H., Wakayama, T., Shimizu, T., Sugiura, T., Iseki, S., & Kato, Y. (2012). Functional expression of carnitine/organic cation transporter OCTN1 in mouse brain neurons: possible involvement in neuronal differentiation. Neurochemistry International, 61(7), 1121-32. https://doi.org/10.1016/j.neuint.2012.08.004
Nakamichi N, et al. Functional Expression of Carnitine/organic Cation Transporter OCTN1 in Mouse Brain Neurons: Possible Involvement in Neuronal Differentiation. Neurochem Int. 2012;61(7):1121-32. PubMed PMID: 22944603.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional expression of carnitine/organic cation transporter OCTN1 in mouse brain neurons: possible involvement in neuronal differentiation. AU - Nakamichi,Noritaka, AU - Taguchi,Takayuki, AU - Hosotani,Hiroshi, AU - Wakayama,Tomohiko, AU - Shimizu,Takuya, AU - Sugiura,Tomoko, AU - Iseki,Shoichi, AU - Kato,Yukio, Y1 - 2012/08/27/ PY - 2012/04/20/received PY - 2012/08/07/revised PY - 2012/08/10/accepted PY - 2012/9/5/entrez PY - 2012/9/5/pubmed PY - 2013/6/6/medline SP - 1121 EP - 32 JF - Neurochemistry international JO - Neurochem Int VL - 61 IS - 7 N2 - The aim of the present study is to clarify the functional expression and physiological role in brain neurons of carnitine/organic cation transporter OCTN1/SLC22A4, which accepts the naturally occurring antioxidant ergothioneine (ERGO) as a substrate in vivo. After intracerebroventricular administration, the distribution of [(3)H]ERGO in several brain regions of octn1(-/-) mice was much lower than that in wild-type mice, whereas extracellular marker [(14)C]mannitol exhibited similar distribution in the two strains. The [(3)H]ERGO distribution in wild-type mice was well correlated with the amount of ERGO derived from food intake and the OCTN1 mRNA level in each brain region. Immunohistochemical analysis revealed colocalization of OCTN1 with neuronal cell markers microtubule-associated protein 2 (MAP2) and βIII-tubulin in mouse brain and primary cultured cortical neurons, respectively. Moreover, cultured cortical neurons exhibited time-dependent and saturable uptake of [(3)H]ERGO. These results demonstrate that OCTN1 is functionally expressed in brain neurons. The addition of ERGO simultaneously with serum to culture medium of cortical neurons attenuated mRNA and protein expressions of MAP2, βIII-tubulin and synapse formation marker synapsin I, and induced those of sex determining region Y-box 2 (Sox2), which is required to maintain the properties of undifferentiated neural stem cells. In neuronal model Neuro2a cells, knockdown of OCTN1 by siRNA reduced the uptake of [(3)H]ERGO with concomitant up-regulation of oxidative stress marker HO-1 and Sox2, and down-regulation of neurite outgrowth marker GAP43. Interestingly, the siRNA knockdown decreased the number of differentiated Neuro2a cells showing long neurites, but increased the total number of cells. Thus, OCTN1 is involved in cellular differentiation, but inhibits their proliferation, possibly via the regulation of cellular oxidative stress. This is the first evidence that OCTN1 plays a role in neuronal differentiation and proliferation, which are required for brain development. SN - 1872-9754 UR - https://www.unboundmedicine.com/medline/citation/22944603/Functional_expression_of_carnitine/organic_cation_transporter_OCTN1_in_mouse_brain_neurons:_possible_involvement_in_neuronal_differentiation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-0186(12)00255-0 DB - PRIME DP - Unbound Medicine ER -