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Pax6 affects Ras-Raf-ERK1/2 in mouse aging brain

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Abstract

Pax6, a transcription factor and multifunctional protein, changes during aging. It also interacts with regulator proteins involved in cell metabolism and survival signalling pathways including Ras-GAP. Many forms of Ras, Raf and ERK1/2 are known but information on their region-specific expression patterns are unavailable from brain during aging. Therefore, it has been intended to evaluate expressions of Pax6 and forms of Ras, Raf, ERK1/2 in hippocampus, caudate nucleus, amygdale, cerebral cortex, cerebellum and olfactory lobe. Association of Pax6 with Ras, Raf and ERK1/2 was evaluated in co-culture (PC-12, C6-glia, U-87 MG) of neuroglia cell lines. Impacts of Pax6 were evaluated by siRNA mediated knockdown and expression patterns Ras-Raf-Erk1/2. Analysis of activities of Pax6 and impacts of 5′AMP, wild-type and mutant ERK were done by RT-PCR and luciferase reporter assay. Results indicate age-dependent changes of Pax6, Ras, Raf, ERK1/2 in different regions of brain of young and old mice. Erk1/2 shows synergistic activities to Pax6.

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Abbreviations

HP:

Hippocampus

C:

Cerebellum

CC:

Cerebral cortex

A:

Amygdale

CN:

Caudate nucleus

OL:

Olfactory lobe

ERK1/2:

Extracellular regulated kinase1/2

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Acknowledgements

RM acknowledges major financial support from ICMR (54/2/CFP/GER/2011-NCD-II), New Delhi, minor supports from IoE BHU. CSIR-Direct-SRF fellowship (09/013(0769)/2018-EMR-I to KS is also acknowledged. We also acknowledge suggestions of Prof A. K. Singh (Department of Zoology, Banaras Hindu University, Varanasi) related to statistical analysis. We also acknowledge to Dr. Sachin Shukla (Department of Zoology, Banaras Hindu University, Varanasi) for designing RT-PCR primers. We would like to give thanks to Prof. David Engelberg and Karin Smorodinskyfor providing the ERK1 and ERK2 wild and mutant type constructs from National University of Singapore.

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Contributions

KS: Methodology, investigation, results analysis, compiled data, writing—manuscript. RM: Planning and supervision from the initiation of experiemnts to completion of the manuscript, reviewing and editing.

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Correspondence to Rajnikant Mishra.

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The authors declare no competing interests.

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Srivastava, K., Mishra, R. Pax6 affects Ras-Raf-ERK1/2 in mouse aging brain. Biogerontology 24, 901–912 (2023). https://doi.org/10.1007/s10522-023-10044-z

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  • DOI: https://doi.org/10.1007/s10522-023-10044-z

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