When cytokinin, a plant hormone, meets the adenosine A2A receptor

A novel neuroprotectant and lead for treating neurodegenerative disorders?

Yi Chao Lee, Ying Chen Yang, Chuen Lin Huang, Tsun Yung Kuo, Jung Hsin Lin, De Ming Yang, Nai Kuei Huang

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

It is well known that cytokinins are a class of phytohormones that promote cell division in plant roots and shoots. However, their targets, biological functions, and implications in mammalian systems have rarely been examined. In this study, we show that one cytokinin, zeatin riboside, can prevent pheochromocytoma (PC12) cells from serum deprivation-induced apoptosis by acting on the adenosine A2A receptor (A2A-R), which was blocked by an A2A-R antagonist and a protein kinase A (PKA) inhibitor, demonstrating the functional ability of zeatin riboside by mediating through A2A-R signaling event. Since the A2A-R was implicated as a therapeutic target in treating Huntington's disease (HD), a cellular model of HD was applied by transfecting mutant huntingtin in PC12 cells. By using filter retardation assay and confocal microscopy we found that zeatin riboside reversed mutant huntingtin (Htt)-induced protein aggregations and proteasome deactivation through A2A-R signaling. PKA inhibitor blocked zeatin riboside-induced suppression of mutant Htt aggregations. In addition, PKA activated proteasome activity and reduced mutant Htt protein aggregations. However, a proteasome inhibitor blocked both zeatin riboside-and PKA activator-mediated suppression of mutant Htt aggregations, confirming mediation of the A2A-R/PKA/proteasome pathway. Taken together, zeatin riboside might have therapeutic potential as a novel neuroprotectant and a lead for treating neurodegenerative disorders.

Original languageEnglish
Article numbere38865
JournalPLoS One
Volume7
Issue number6
DOIs
Publication statusPublished - Jun 18 2012

Fingerprint

Adenosine A2A Receptors
Cytokinins
Plant Growth Regulators
neurodegenerative diseases
zeatin
Neuroprotective Agents
adenosine
cAMP-dependent protein kinase
Neurodegenerative Diseases
plant hormones
cytokinins
Cyclic AMP-Dependent Protein Kinases
proteasome endopeptidase complex
receptors
Proteasome Endopeptidase Complex
Agglomeration
mutants
PC12 Cells
Huntington Disease
Mutant Proteins

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

When cytokinin, a plant hormone, meets the adenosine A2A receptor : A novel neuroprotectant and lead for treating neurodegenerative disorders? / Lee, Yi Chao; Yang, Ying Chen; Huang, Chuen Lin; Kuo, Tsun Yung; Lin, Jung Hsin; Yang, De Ming; Huang, Nai Kuei.

In: PLoS One, Vol. 7, No. 6, e38865, 18.06.2012.

Research output: Contribution to journalArticle

Lee, Yi Chao ; Yang, Ying Chen ; Huang, Chuen Lin ; Kuo, Tsun Yung ; Lin, Jung Hsin ; Yang, De Ming ; Huang, Nai Kuei. / When cytokinin, a plant hormone, meets the adenosine A2A receptor : A novel neuroprotectant and lead for treating neurodegenerative disorders?. In: PLoS One. 2012 ; Vol. 7, No. 6.
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