Mitochondrial nucleoid remodeling and biogenesis are regulated by the p53-p21WAF1-PKCζ pathway in p16INK4a-silenced cells

Lee, Yun Yeong; Choi, Yeon Seung; Kim, Do Wan; Cheong, Jae Youn; Song, Kye Yong; Ryu, Min Sook; Lim, In Kyoung

doi:10.18632/aging.103029

Cited by 7 publications

(6 citation statements)

References 46 publications

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“…P53 regulates mitochondrial homeostasis and biogenesis [ 129 , 130 ]. Asthmatic patients exert an increased expression of P53 in BSM and decreased Mdm2/P53 interaction, due to phosphorylation of P53 at Ser20.…”

Section: Copdmentioning

confidence: 99%

P53 in the impaired lungs

Uddin

Barabutis

2020

DNA Repair

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Our laboratory is focused on investigating the supportive role of P53 towards the maintenance of lung homeostasis. Acute lung injury, acute respiratory distress syndrome, chronic obstructive pulmonary disease, pulmonary fibrosis, bronchial asthma, pulmonary arterial hypertension, pneumonia and tuberculosis are respiratory pathologies, associated with dysfunctions of this endothelium defender (P53). Herein we review the evolving role of P53 towards the aforementioned inflammatory disorders, to potentially reveal new therapeutic possibilities in pulmonary disease.

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Section: Copdmentioning

confidence: 99%

P53 in the impaired lungs

Uddin

Barabutis

2020

DNA Repair

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“…The cell cycle regulator p53-p21 WAF1/Cip1 is induced by DNA damage and proliferative arrest, and is a main driver of apoptosis [ 29 , 30 ]. In our in vitro mechanism study, we established a SIPS auditory hair cell model as described in our previous study [ 31 ], and made observations for 5 days after treatment with a low-dose DOXO (100 ng/mL), a DNA damage reagent. We found that C-cas3 expression increased as HSF1 decreased after 3 days, which was consistent with our in vivo results ( Figure 2 A).…”

Section: Resultsmentioning

confidence: 99%

Heat Shock Factor 1 Prevents Age-Related Hearing Loss by Decreasing Endoplasmic Reticulum Stress

Lee

Gil

Jeong

et al. 2021

Cells

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Endoplasmic reticulum (ER) stress is a common stress factor during the aging process. Heat shock factor 1 (HSF1) plays a critical role in ER stress; however, its exact function in age-related hearing loss (ARHL) has not been fully elucidated. The purpose of the present study was to identify the role of HSF1 in ARHL. In this study, we demonstrated that the loss of inner and outer hair cells and their supporting cells was predominant in the high-frequency region (basal turn, 32 kHz) in ARHL cochleae. In the aging cochlea, levels of the ER stress marker proteins p-eIF2α and CHOP increased as HSF1 protein levels decreased. The levels of various heat shock proteins (HSPs) also decreased, including HSP70 and HSP40, which were markedly downregulated, and the expression levels of Bax and cleaved caspase-3 apoptosis-related proteins were increased. However, HSF1 overexpression showed significant hearing protection effects in the high-frequency region (basal turn, 32 kHz) by decreasing CHOP and cleaved caspase-3 and increasing the HSP40 and HSP70 proteins. These findings were confirmed by HSF1 functional studies using an auditory cell model. Therefore, we propose that HSF1 can function as a mediator to prevent ARHL by decreasing ER stress-dependent apoptosis in the aging cochlea.

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“…In addition, elevated P53, P21, and P27 were observed in RGC-5 cells transfected with c.977C>T mutation. P53 and its primary target P21 is linked with DNA damage to cell cycle arrest [ 23 – 24 ]. P27 is a negative regulator of cell proliferation and arrests the cell cycle by inhibiting cyclin-dependent kinases [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

A novel mutation in PCK2 gene causes primary angle-closure glaucoma

Yang

Sun

et al. 2021

Aging

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Primary angle-closure glaucoma (PACG) is an ophthalmic genetic disease characterized by direct contact between the iris and trabecular meshwork, resulting in an obstructed outflow of aqueous humor from the eye. However, it is unclear as to what role genetics plays in the development of PACG. The present study investigated the disease-causing mutation in a five-generation Chinese PACG family using whole-genome sequencing. A novel heterozygous missense mutation c.977C>T in PCK2 gene was identified in five affected family members, but not in any unaffected and 86 unrelated healthy individuals. This nucleotide substitute is predicted to result in a proline to leucine substitution p.Pro326Leu. Furthermore, the function of this mutation was analyzed through various in vitro assays using the RGC-5 cell line. Our results demonstrate that the p.Pro326Leu mutation induces RGC-5 cell cycle arrest and apoptosis with a decreased BcL-XL. The increasing P53, P27, P21, AKT, and P-GSK3α were also detected in the cells transfected with c.977C>T mutation, suggesting that this mutation within PCK2 gene cause PACG through impairment of AKT/GSK3α signaling pathway.

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Mitochondrial nucleoid remodeling and biogenesis are regulated by the p53-p21WAF1-PKCζ pathway in p16INK4a-silenced cells

Cited by 7 publications

References 46 publications

P53 in the impaired lungs

P53 in the impaired lungs

Heat Shock Factor 1 Prevents Age-Related Hearing Loss by Decreasing Endoplasmic Reticulum Stress

A novel mutation in PCK2 gene causes primary angle-closure glaucoma

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