Clostridium perfringens phospholipase C impairs innate immune response by inducing integrated stress response and mitochondrial-induced epigenetic modifications

Bunkar, Neha; Sharma, Jahnavi; Chouksey, Anju; Kumari, Roshani; Gupta, P. K.; Tiwari, Rajnarayan R; Lodhi, Lalit; Srivastava, Rupesh K.; Bhargava, Arpit; Mishra, Pradyumna Kumar

doi:10.1016/j.cellsig.2020.109776

Cited by 8 publications

(4 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Though the four miRNAs we found in this study did not target BACE1 directly, they all associated with STAT1 that regulates BACE1, therefore there might be a potential connection. MitomiRs are a subset of miRNAs found to be localized to human mitochondria and potentially regulate mitochondrial function under the physiological and pathological conditions of AD 72 , interestingly 3/4 miRNAs (miR-3651, miR-664b-3p and miRNA-150-5p) in our study were all mitomiRs 73 – 75 , which might suggested a potential role of these miRNAs in AD.…”

Section: Discussionmentioning

confidence: 48%

Lead-exposure associated miRNAs in humans and Alzheimer’s disease as potential biomarkers of the disease and disease processes

Wen

Verheijen

Wittens

et al. 2022

Sci Rep

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is a neurodegenerative disease that eventually affects memory and behavior. The identification of biomarkers based on risk factors for AD provides insight into the disease since the exact cause of AD remains unknown. Several studies have proposed microRNAs (miRNAs) in blood as potential biomarkers for AD. Exposure to heavy metals is a potential risk factor for onset and development of AD. Blood cells of subjects that are exposed to lead detected in the circulatory system, potentially reflect molecular responses to this exposure that are similar to the response of neurons. In this study we analyzed blood cell-derived miRNAs derived from a general population as proxies of potentially AD-related mechanisms triggered by lead exposure. Subsequently, we analyzed these mechanisms in the brain tissue of AD subjects and controls. A total of four miRNAs were identified as lead exposure-associated with hsa-miR-3651, hsa-miR-150-5p and hsa-miR-664b-3p being negatively and hsa-miR-627 positively associated. In human brain derived from AD and AD control subjects all four miRNAs were detected. Moreover, two miRNAs (miR-3651, miR-664b-3p) showed significant differential expression in AD brains versus controls, in accordance with the change direction of lead exposure. The miRNAs’ gene targets were validated for expression in the human brain and were found enriched in AD-relevant pathways such as axon guidance. Moreover, we identified several AD relevant transcription factors such as CREB1 associated with the identified miRNAs. These findings suggest that the identified miRNAs are involved in the development of AD and might be useful in the development of new, less invasive biomarkers for monitoring of novel therapies or of processes involved in AD development.

show abstract

Section: Discussionmentioning

confidence: 48%

Lead-exposure associated miRNAs in humans and Alzheimer’s disease as potential biomarkers of the disease and disease processes

Wen

Verheijen

Wittens

et al. 2022

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Thus, phosphorylated eIF2α assists the translation of specific mRNAs to activate ATF4, which then interacts with ATF3 and CHOP to maintain cellular homeostasis [28,29]. Earlier studies have reported that disturbances in the mitochondrial integrity are closely associated with the induction of ISR [18]. In the current study, the relative quantitative expression of OMA1, DELE1, and HRI genes exhibited modified profiles in the older age risk group.…”

Section: Discussionmentioning

confidence: 51%

“…GAPDH was used as an internal control. After the completion of the PCR cycles, Ct values were obtained, and fold change was calculated by using the ddCt method [18].…”

Section: Methodsmentioning

confidence: 99%

Molecular insights into mitoepigenetic stress response signaling in age-associated cardiovascular disease risk

Soni,

Kaur,

Gurjar

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Cardiovascular diseases (CVD) represent a major challenge for the elderly population and continue to be among the leading causes of mortality worldwide. The integrity of mitochondria in peripheral lymphocytes can indicate age-related degenerative disorders, revealing the balance between bioenergetics, inflammation, and senescence. The present study aims to investigate the impact of aging on mitochondrial-mediated epigenetic stress response mechanisms in both young and elderly individuals. Mitochondrial oxidative DNA damage, repair response, copy number, methylation, fusion, fission genes, electron transport chain enzyme complex activities, pro-inflammatory cytokine levels, and associated epigenetic mechanisms were evaluated. The results demonstrate that the elderly group experienced more significant disruption in the expression of mitochondrial genes, leading to impaired mitochondrial DNA (mtDNA) integrity closely linked to mitochondrial-nuclear crosstalk, ultimately increasing their susceptibility to CVD. The findings highlight mitochondria's crucial role in cellular dynamics, influencing stress responses and epigenetic mechanisms through fusion and fission cycles. Overall, these insights provide valuable information about the complex molecular processes linking mitochondrial dysfunction to age-related cardiovascular risks, paving the way for further exploration and potential interventions in aging-related health outcomes.

show abstract

“…And our results showed that exotoxins could induce the death of the THP-1 cells. In addition, there are studies that verified that, following exposure to Clostridium perfringens phospholipase C (CpPLC), a significant generation of mitochondrial ROS was observed, and these disturbances further led to alterations in the mitochondrial genome and functioning [21]. Moreover, the levels of ROS showed a significant increase in CPB2 toxin-induced IPEC-J2 cells [22].…”

Section: Discussionmentioning

confidence: 97%

Injury of Macrophages Induced by Clostridium perfringens Type C Exotoxins

Zhang,

Wang,

Ding

et al. 2024

IJMS

View full text Add to dashboard Cite

Clostridium perfringens is a kind of anaerobic Gram-positive bacterium that widely exists in the intestinal tissue of humans and animals. And the main virulence factor in Clostridium perfringens is its exotoxins. Clostridium perfringens type C is the main strain of livestock disease, its exotoxins can induce necrotizing enteritis and enterotoxemia, which lead to the reduction in feed conversion, and a serious impact on breeding production performance. Our study found that treatment with exotoxins reduced cell viability and triggered intracellular reactive oxygen species (ROS) in human mononuclear leukemia cells (THP-1) cells. Through transcriptome sequencing analysis, we found that the levels of related proteins such as heme oxygenase 1 (HO-1) and ferroptosis signaling pathway increased significantly after treatment with exotoxins. To investigate whether ferroptosis occurred after exotoxin treatment in macrophages, we confirmed that the protein expression levels of antioxidant factors glutathione peroxidase 4/ferroptosis-suppressor-protein 1/the cystine/glutamate antiporter solute carrier family 7 member 11 (GPX4/FSP1/xCT), ferroptosis-related protein nuclear receptor coactivator 4/transferrin/transferrin receptor (NCOA4/TF/TFR)/ferritin and the level of lipid peroxidation were significantly changed. Based on the above results, our study suggested that Clostridium perfringens type C exotoxins can induce macrophage injury through oxidative stress and ferroptosis.

show abstract

Clostridium perfringens phospholipase C impairs innate immune response by inducing integrated stress response and mitochondrial-induced epigenetic modifications

Cited by 8 publications

References 82 publications

Lead-exposure associated miRNAs in humans and Alzheimer’s disease as potential biomarkers of the disease and disease processes

Lead-exposure associated miRNAs in humans and Alzheimer’s disease as potential biomarkers of the disease and disease processes

Molecular insights into mitoepigenetic stress response signaling in age-associated cardiovascular disease risk

Injury of Macrophages Induced by Clostridium perfringens Type C Exotoxins

Contact Info

Product

Resources

About