Identification of protease serine S1 family member 53 as a mitochondrial protein in murine islet beta cells

Mizusawa, Noriko; Harada, Nagakatsu; Iwata, Takeo; Ohigashi, Izumi; Itakura, Mitsuo; Yoshimoto, Katsuhiko

doi:10.1080/19382014.2021.1982325

Cited by 4 publications

(4 citation statements)

References 53 publications

(56 reference statements)

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“…We identified new markers specific for an individual β-cell state and conserved across all datasets mapping to that state, with top markers highlighted in Figure 5c ( Supplementary Table S4 , more detailed description is in Supplementary Note S4 ). For example, we identified a new marker of healthy adult state Prss53 , associated with mitochondrial function 99 .…”

Section: Resultsmentioning

confidence: 99%

Delineating mouse β-cell identity during lifetime and in diabetes with a single cell atlas

Hrovatin

Bastidas-Ponce

Bakhti

et al. 2022

Preprint

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Multiple single-cell RNA sequencing (scRNA-seq) datasets have been generated to study pancreatic islet cells during development, homeostasis, and diabetes progression. However, despite the time and resources invested into the past scRNA-seq studies, there is still no consensus on islet cell states and associated pathways in health and dysfunction as well as the value of frequently used preclinical mouse diabetes models. Since these challenges can be only resolved with a joint analysis of multiple datasets, we present a scRNA-seq cross-condition mouse islet atlas (MIA). We integrated over 300,000 cells from nine datasets with 56 samples, varying in age, sex, and diabetes models, including autoimmune type 1 diabetes (T1D) model (NOD), gluco-/lipotoxicity T2D model (db/db), and chemical streptozotocin (STZ) β-cell ablation model. MIA is a curated resource that enables interactive exploration of gene expression and transfer of cell types and states. We use MIA to obtain new insights into islet cells in health and disease that cannot be reached from individual datasets. Based on the MIA β-cell landscape we report cross-publication differences between previously suggested marker genes of individual phenotypes. We further show that in the STZ model β-cells transcriptionally correlate to human T2D and mouse db/db model β-cells, but are less similar to human T1D and mouse NOD model β-cells. We define new cell states involved in disease progression across diabetes models. We also observe different pathways shared between immature, aged, and diabetes model β-cell states. In conclusion, our work presents the first comprehensive analysis of β-cell responses to different stressors, providing a roadmap for the understanding of β-cell plasticity, compensation, and demise.

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Section: Resultsmentioning

confidence: 99%

Delineating mouse β-cell identity during lifetime and in diabetes with a single cell atlas

Hrovatin

Bastidas-Ponce

Bakhti

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…The protein encoded by DUSP1 is a phosphatase with dual specificity for tyrosine and threonine, and DUSP1 can dephosphorylate the MAP kinase MAPK1/ERK2, which results in its involvement in several cellular processes [35]. PRSS53 has been demonstrated to enhance serine-type endopeptidase activity, which is involved in protein hydrolysis [36]. The expression of DUSP1 and PRSS53 can be reduced in the pituitary by treatment with the SS-14 DNA vaccine, which in turn regulates amino acids that are important in nutrient metabolism processes.…”

Section: A C C E P T E D a R T I C L Ementioning

confidence: 99%

Immunisation of the somatostatin gene alters hypothalamic-pituitary-liver gene expressions and enhances growth in Dazu black goats

Qin,

Fang,

Song

et al. 2024

Anim Biosci

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“…048-33575) and fluorescence intensities of both red (JC-1 aggregates) and green (JC-1 monomers) were recorded using a fluorescence microplate reader (Tecan Group Ltd., Männedorf, Switzerland, Catalog no. INFINITE M200 PRO), 26 f luorescence intensity of Ex/Em = 535/590 nm and Ex/Em = 485/535 nm is determined for red and green, respectively. Alterations in the red and green fluorescence intensity indicated changes in the mitochondrial membrane potential.…”

Section: Evaluation Of Mitochondrial Membrane Potentialmentioning

confidence: 99%

Mitochondrial Responses to Sublethal Doxorubicin in H9c2 Cardiomyocytes: The Role of Phosphorylated CaMKII

Priyono,

Miake,

Sawano

et al. 2024

Yonago Acta Med.

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Background Doxorubicin (Dox) is effective against different types of cancers, but it poses cardiotoxic side effects, frequently resulting in irreversible heart failure. However, the complexities surrounding this cardiotoxicity, especially at sublethal dosages, remain to be fully elucidated. We investigated early cellular disruptions in response to sublethal Dox, with a specific emphasis on the role of phosphorylated calcium/calmodulindependent protein kinase II (CaMKII) in initiating mitochondrial dysfunction. Methods This study utilized the H9c2 cardiomyocyte model to identify a sublethal concentration of Dox and investigate its impact on mitochondrial health using markers such as mitochondrial membrane potential (MMP), mitophagy initiation, and mitochondrial calcium dynamics. We examined the roles of and interactions between CaMKII, dynamin-related protein 1 (Drp1), and the mitochondrial calcium uniporter (MCU) in Dox-induced mitochondrial disruption using specific inhibitors, such as KN-93, Mdivi-1, and Ru360, respectively. Results Exposure to a sublethal dose of Dox reduced the MMP red-to-green fluorescence ratio in H9c2 cells by 40.6% compared with vehicle, and increased the proportion of cells undergoing mitophagy from negligible levels compared with vehicle to 62.2%. Mitochondrial calcium levels also increased by 8.7-fold compared with the vehicle group. Notably, the activation of CaMKII, particularly its phosphorylated form, was pivotal in driving these mitochondrial changes, as inhibition using KN-93 restored MMP and decreased mitophagy. However, inhibition of Drp1 and MCU functions had a limited impact on the observed mitochondrial disruptions. Conclusion Sublethal administration of Dox is closely linked to CaMKII activation through phosphorylation, emphasizing its pivotal role in early mitochondrial disruption. These findings present a promising direction for developing therapeutic strategies that may alleviate the cardiotoxic effects of Dox, potentially increasing its clinical efficacy.

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Identification of protease serine S1 family member 53 as a mitochondrial protein in murine islet beta cells

Cited by 4 publications

References 53 publications

Delineating mouse β-cell identity during lifetime and in diabetes with a single cell atlas

Delineating mouse β-cell identity during lifetime and in diabetes with a single cell atlas

Immunisation of the somatostatin gene alters hypothalamic-pituitary-liver gene expressions and enhances growth in Dazu black goats

Mitochondrial Responses to Sublethal Doxorubicin in H9c2 Cardiomyocytes: The Role of Phosphorylated CaMKII

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