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Activation of cyclin D1 affects mitochondrial mass following traumatic brain injury.

ABSTRACT: Cell cycle activation has been associated with varying types of neurological disorders including brain injury. Cyclin D1 is a critical modulator of cell cycle activation and upregulation of Cyclin D1 in neurons contributes to the pathology associated with traumatic brain injury (TBI). Mitochondrial mass is a critical factor to maintain the mitochondrial function, and it can be regulated by different signaling cascades and transcription factors including NRF1. However, the underlying mechanism of how TBI leads to impairment of mitochondrial mass following TBI remains obscure. Our results indicate that augmentation of CyclinD1 attenuates mitochondrial mass formation following TBI. To elucidate the molecular mechanism, we found that Cyclin D1 interacts with a transcription factor NRF1 in the nucleus and prevents NRF1's interaction with p300 in the pericontusional cortex following TBI. As a result, the acetylation level of NRF1 was decreased, and its transcriptional activity was attenuated. This event leads to a loss of mitochondrial mass in the pericontusional cortex following TBI. Intranasal delivery of Cyclin D1 RNAi immediately after TBI rescues transcriptional activation of NRF1 and recovers mitochondrial mass after TBI.

SUBMITTER: Saha P

PROVIDER: S-EPMC6087674 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Activation of cyclin D1 affects mitochondrial mass following traumatic brain injury.

Saha Pampa P Gupta Rajaneesh R Sen Tanusree T Sen Nilkantha N

Neurobiology of disease 20180718

Cell cycle activation has been associated with varying types of neurological disorders including brain injury. Cyclin D1 is a critical modulator of cell cycle activation and upregulation of Cyclin D1 in neurons contributes to the pathology associated with traumatic brain injury (TBI). Mitochondrial mass is a critical factor to maintain the mitochondrial function, and it can be regulated by different signaling cascades and transcription factors including NRF1. However, the underlying mechanism of ...[more]

PMID: 30010002

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Activation of cyclin D1 affects mitochondrial mass following traumatic brain injury.

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Activation of cyclin D1 affects mitochondrial mass following traumatic brain injury.

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