Branched-Chain Amino Acids Deficiency Promotes Diabetic Neuropathic Pain Through Upregulating LAT1 and Inhibiting Kv1.2 Channel.

Kv1.2 L‐type amino acid transporter 1 branched‐chain amino acids diabetic neuropathic pain

Journal

Advanced science (Weinheim, Baden-Wurttemberg, Germany)
ISSN: 2198-3844
Titre abrégé: Adv Sci (Weinh)
Pays: Germany
ID NLM: 101664569

Informations de publication

Date de publication:
01 Jul 2024
Historique:
revised: 18 06 2024
received: 27 02 2024
medline: 1 7 2024
pubmed: 1 7 2024
entrez: 1 7 2024
Statut: aheadofprint

Résumé

Diabetic neuropathic pain (DNP), one of the most common complications of diabetes, is characterized by bilateral symmetrical distal limb pain and substantial morbidity. To compare the differences  is aimed at serum metabolite levels between 81 DNP and 73 T2DM patients without neuropathy and found that the levels of branched-chain amino acids (BCAA) are significantly lower in DNP patients than in T2DM patients. In high-fat diet/low-dose streptozotocin (HFD/STZ)-induced T2DM and leptin receptor-deficient diabetic (db/db) mouse models, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated DNP symptoms. Mechanistically, using a combination of RNA sequencing of mouse dorsal root ganglion (DRG) tissues and label-free quantitative proteomic analysis of cultured cells, it is found that BCAA deficiency activated the expression of L-type amino acid transporter 1 (LAT1) through ATF4, which is reversed by BCAA supplementation. Abnormally upregulated LAT1 reduced Kv1.2 localization to the cell membrane, and inhibited Kv1.2 channels, thereby increasing neuronal excitability and causing neuropathy. Furthermore, intraperitoneal injection of the LAT1 inhibitor, BCH, alleviated DNP symptoms in mice, confirming that BCAA-deficiency-induced LAT1 activation contributes to the onset of DNP. These findings provide fresh insights into the metabolic differences between DNP and T2DM, and the development of approaches for the management of DNP.

Identifiants

pubmed: 38946582
doi: 10.1002/advs.202402086
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2402086

Subventions

Organisme : Key Development Programs of Basic Research of China
ID : Nos. 2020YFA0803601
Organisme : Key Development Programs of Basic Research of China
ID : 2019YFA0801900
Organisme : National Natural Science Foundation of China
ID : 82330048
Organisme : National Natural Science Foundation of China
ID : 82170236
Organisme : National Natural Science Foundation of China
ID : 81700212
Organisme : National Natural Science Foundation of China
ID : 32370824
Organisme : National Natural Science Foundation of China
ID : 32000895
Organisme : National Natural Science Foundation of China
ID : 82300428
Organisme : Program of Shanghai Academic Research Leader
ID : 21XD1421700
Organisme : Innovation Program of the Shanghai Municipal Education Commission
ID : 2023ZKZD24
Organisme : Shanghai Sailing Program
ID : 23YF1425500
Organisme : Innovative research team of high-level local universities in Shanghai
ID : SHSMU-ZDCX20211100

Informations de copyright

© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.

Références

A. S. Shah, K. J. Nadeau, Diabetologia 2020, 63, 683.
J. Wei, J. Tian, C. Tang, X. Fang, R. Miao, H. Wu, X. Wang, X. Tong, J. Diabetes Res. 2022, 2022, 3448618.
E. L. Feldman, B. C. Callaghan, R. Pop‐Busui, D. W. Zochodne, D. E. Wright, D. L. Bennett, V. Bril, J. W. Russell, V. Viswanathan, Nat. Rev. Dis. Primers 2019, 5, 41.
L. Ang, M. Jaiswal, C. Martin, R. Pop‐Busui, Curr. Diab. Rep. 2014, 14, 528.
C. D. S. Branch Group of Neurological Complications, Chinese Journal of Endocrinology and Metabolism 2021, 37, 499.
E. L. Feldman, K. A. Nave, T. S. Jensen, D. L. H. Bennett, Neuron 2017, 93, 1296.
B. C. Callaghan, A. A. Little, E. L. Feldman, R. A. Hughes, Cochrane Database Syst. Rev. 2012, 6, CD007543.
F. Ismail‐Beigi, T. Craven, M. A. Banerji, J. Basile, J. Calles, R. M. Cohen, R. Cuddihy, W. C. Cushman, S. Genuth, R. H. Grimm Jr., B. P. Hamilton, B. Hoogwerf, D. Karl, L. Katz, A. Krikorian, P. O'Connor, R. Pop‐Busui, U. Schubart, D. Simmons, H. Taylor, A. Thomas, D. Weiss, I. Hramiak, A. group, Lancet 2010, 376, 419.
M. Charles, N. Ejskjaer, D. R. Witte, K. Borch‐Johnsen, T. Lauritzen, A. Sandbaek, Diabetes Care 2011, 34, 2244.
M. Neinast, D. Murashige, Z. Arany, Annu. Rev. Physiol. 2019, 81, 139.
P. J. White, C. B. Newgard, Science 2019, 363, 582.
C. J. Lynch, S. H. Adams, Nat. Rev. Endocrinol. 2014, 10, 723.
D. C. Tarlungeanu, E. Deliu, C. P. Dotter, M. Kara, P. C. Janiesch, M. Scalise, M. Galluccio, M. Tesulov, E. Morelli, F. M. Sonmez, K. Bilguvar, R. Ohgaki, Y. Kanai, A. Johansen, S. Esharif, T. Ben‐Omran, M. Topcu, A. Schlessinger, C. Indiveri, K. E. Duncan, A. O. Caglayan, M. Gunel, J. G. Gleeson, G. Novarino, Cell 2016, 167, 1481.
L. S. Knaus, B. Basilico, D. Malzl, M. Gerykova Bujalkova, M. Smogavec, L. A. Schwarz, S. Gorkiewicz, N. Amberg, F. M. Pauler, C. Knittl‐Frank, M. Tassinari, N. Maulide, T. Rulicke, J. Menche, S. Hippenmeyer, G. Novarino, Cell 2023, 186, 1950.
Y. Kanai, H. Segawa, K. Miyamoto, H. Uchino, E. Takeda, H. Endou, J. Biol. Chem. 1998, 273, 23629.
F. Verrey, E. I. Closs, C. A. Wagner, M. Palacin, H. Endou, Y. Kanai, Pflugers Arch 2004, 447, 532.
Q. Wang, C. G. Bailey, C. Ng, J. Tiffen, A. Thoeng, V. Minhas, M. L. Lehman, S. C. Hendy, G. Buchanan, C. C. Nelson, J. E. Rasko, J. Holst, Cancer Res. 2011, 71, 7525.
O. Yanagida, Y. Kanai, A. Chairoungdua, D. K. Kim, H. Segawa, T. Nii, S. H. Cha, H. Matsuo, J. Fukushima, Y. Fukasawa, Y. Tani, Y. Taketani, H. Uchino, J. Y. Kim, J. Inatomi, I. Okayasu, K. Miyamoto, E. Takeda, T. Goya, H. Endou, Biochim. Biophys. Acta 2001, 1514, 291.
R. Yan, X. Zhao, J. Lei, Q. Zhou, Nature 2019, 568, 127.
K. G. Hewton, A. S. Johal, S. J. Parker, Metabolites 2021, 11, 112.
X. Zhang, L. Liu, W. C. Chen, F. Wang, Y. R. Cheng, Y. M. Liu, Y. F. Lai, R. J. Zhang, Y. N. Qiao, Y. Y. Yuan, Y. Lin, W. Xu, J. Cao, Y. H. Gui, J. Y. Zhao, Adv. Sci. 2022, 9, e2201034.
R. Zhao, K. Cai, J. J. Yang, Q. Zhou, W. Cao, J. Xiang, Y. H. Shen, L. L. Cheng, W. D. Zang, Y. Lin, Y. Y. Yuan, W. Xu, H. Tao, S. M. Zhao, J. Y. Zhao, Cell Rep. 2023, 42, 112400.
X. H. Wang, S. Xu, X. Y. Zhou, R. Zhao, Y. Lin, J. Cao, W. D. Zang, H. Tao, W. Xu, M. Q. Li, S. M. Zhao, L. P. Jin, J. Y. Zhao, Nat. Commun. 2021, 12, 3428.
R. Wang, Z. Qiu, G. Wang, Q. Hu, N. Shi, Z. Zhang, Y. Wu, C. Zhou, Eur. J. Pharmacol. 2020, 882, 173266.
S. Liu, X. Liu, H. Xiong, W. Wang, Y. Liu, L. Yin, C. Tu, H. Wang, X. Xiang, J. Xu, B. Duan, A. Tao, Z. Zhao, Z. Mei, Brain Behav. Immun. 2019, 80, 711,.
T. B. Salisbury, S. Arthur, Int. J. Mol. Sci. 2018, 19, 2373.
D. Mossmann, S. Park, M. N. Hall, Nat. Rev. Cancer 2018, 18, 744.
V. A. Baronas, R. Y. Yang, L. C. Morales, S. Sipione, H. T. Kurata, Nat. Commun. 2018, 9, 4417.
S. M. Lamothe, H. T. Kurata, J. Gen. Physiol. 2020, 152, e201912524.
S. M. Lamothe, N. Sharmin, G. Silver, M. Satou, Y. Hao, T. Tateno, V. A. Baronas, H. T. Kurata, Elife 2020, 9, https://doi.org/10.7554/eLife.54916.
T. Fujita, I. Utsunomiya, J. Ren, Y. Matsushita, M. Kawai, S. Sasaki, K. Hoshi, T. Miyatake, K. Taguchi, Neurochem. Res. 2006, 31, 589.
S. Yothaisong, H. Dokduang, N. Anzai, K. Hayashi, N. Namwat, P. Yongvanit, S. Sangkhamanon, P. Jutabha, H. Endou, W. Loilome, Tumour Biol. 2017, 39, 101042831769454.
G. Pathria, S. Verma, J. Yin, D. A. Scott, Z. A. Ronai, EMBO Rep. 2021, 22, e51436.
K. J. Lohkamp, A. M. van den Hoek, G. Sole‐Guardia, M. Lisovets, T. Alves Hoffmann, K. Velanaki, B. Geenen, V. Verweij, M. C. Morrison, R. Kleemann, M. Wiesmann, A. J. Kiliaan, Nutrients 2023, 15, 1716.
S. R. A. Alles, K. Gomez, A. Moutal, R. Khanna, Neurobiol. Pain 2020, 8, 100050.
A. E. Goins, K. Gomez, D. Ran, M. Afaghpour‐Becklund, R. Khanna, S. R. A. Alles, Pflugers Arch. 2022, 474, 397.
P. D. O'Brien, S. A. Sakowski, E. L. Feldman, ILAR J. 2014, 54, 259.
C. G. Jolivalt, K. E. Frizzi, L. Guernsey, A. Marquez, J. Ochoa, M. Rodriguez, N. A. Calcutt, Curr. Protoc. Mouse Biol. 2016, 6, 223.
T. A. Lutz, Nat. Rev. Endocrinol. 2023, 19, 350.
W. Zhang, N. Zhuang, X. Liu, L. He, Y. He, P. Mahinthichaichan, H. Zhang, Y. Kang, Y. Lu, Q. Wu, D. Xu, L. Shi, Cell Mol. Immunol. 2020, 17, 1063.
R. Ravindran, J. Loebbermann, H. I. Nakaya, N. Khan, H. Ma, L. Gama, D. K. Machiah, B. Lawson, P. Hakimpour, Y. C. Wang, S. Li, P. Sharma, R. J. Kaufman, J. Martinez, B. Pulendran, Nature 2016, 531, 523.
Z. Pan, S. Du, K. Wang, X. Guo, Q. Mao, X. Feng, L. Huang, S. Wu, B. Hou, Y. J. Chang, T. Liu, T. Chen, H. Li, T. Bachmann, A. Bekker, H. Hu, Y. X. Tao, Adv. Sci. (Weinh) 2021, 8, e2004515.
J. Y. Zhao, L. Liang, X. Gu, Z. Li, S. Wu, L. Sun, F. E. Atianjoh, J. Feng, K. Mo, S. Jia, B. M. Lutz, A. Bekker, E. J. Nestler, Y. X. Tao, Nat. Commun. 2017, 8, 14712.
X. Yue, N. Tiwari, L. Zhu, H. D. T. Ngo, J. M. Lim, B. Gim, S. Jing, Y. Wang, Y. Qian, I. Lee, Commun. Biol. 2021, 4, 1370.
J. Zhang, L. Rong, J. Shao, Y. Zhang, Y. Liu, S. Zhao, L. Li, W. Yu, M. Zhang, X. Ren, Q. Zhao, C. Zhu, H. Luo, W. Zang, J. Cao, J. Neurochem. 2021, 156, 367.

Auteurs

Ze-Yu Zhou (ZY)

State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200438, China.
Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.

Ji-Ying Wang (JY)

Department of Pain Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.

Zhi-Xiao Li (ZX)

Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China.

Hong-Li Zheng (HL)

Department of Pain Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.

Ya-Nan Zhou (YN)

Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China.

Li-Na Huang (LN)

Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 20080, China.

Li-Juan Wang (LJ)

Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 20080, China.

Xiao-Wei Ding (XW)

Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.

Xin Sun (X)

Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.

Ke Cai (K)

Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.

Rui Zhao (R)

Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.

Yan Shi (Y)

Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.

Alex F Chen (AF)

Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.

Zhi-Qiang Pan (ZQ)

Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, 221004, China.

Jing Cao (J)

Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China.

Fu-Qing Lin (FQ)

Department of Pain Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.

Jian-Yuan Zhao (JY)

Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.

Classifications MeSH