Investigation of the caspase-dependent mitochondrial apoptotic pathway in mononuclear cells of patients with systemic lupus erythematosus

Su, Yu‐Jih; Cheng, Tien‐Tsai; Chen, Chung‐Jen; Chang, Wen-Neng; Tsai, Nai‐Wen; Kung, Chia-Te; Wang, Hung-Chen; Lin, Wei-Che; Huang, Chih-Cheng; Chang, Ya‐Ting; Su, Chih-Min; Chiang, Yu Chung; Cheng, Ben-Chung; Lin, Yujun; Lu, Cheng-Hsien

doi:10.1186/s12967-014-0303-1

Cited by 15 publications

(10 citation statements)

References 41 publications

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“…Besides, mitochondrial (mt)DNA damage [45,73,74,75,76], characterized by D-310 heteroplasmy and copy number decrease [42,77], is also present in SLE. Su et al [78] investigated the caspase-dependent mitochondrial apoptotic pathway in immune cells from SLE patients. They found that peripheral blood mononuclear cells (PBMCs) and polymorphonuclear neutrophils (PMNs) from SLE patients exhibited increased expression of apoptosis initiators, caspase 9 and 10, that are positively correlated to the expression of mitochondrial anti-viral signaling protein and interferon regulatory factor 7.…”

Section: Mitochondrial Dysfunction Is One Of the Crucial Up-streammentioning

confidence: 99%

Molecular and Cellular Bases of Immunosenescence, Inflammation, and Cardiovascular Complications Mimicking “Inflammaging” in Patients with Systemic Lupus Erythematosus

Tsai

Shen

Liao

et al. 2019

IJMS

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Systemic lupus erythematosus (SLE) is an archetype of systemic autoimmune disease, characterized by the presence of diverse autoantibodies and chronic inflammation. There are multiple factors involved in lupus pathogenesis, including genetic/epigenetic predisposition, sexual hormone imbalance, environmental stimulants, mental/psychological stresses, and undefined events. Recently, many authors noted that “inflammaging”, consisting of immunosenescence and inflammation, is a common feature in aging people and patients with SLE. It is conceivable that chronic oxidative stresses originating from mitochondrial dysfunction, defective bioenergetics, abnormal immunometabolism, and premature telomere erosion may accelerate immune cell senescence in patients with SLE. The mitochondrial dysfunctions in SLE have been extensively investigated in recent years. The molecular basis of normoglycemic metabolic syndrome has been found to be relevant to the production of advanced glycosylated and nitrosative end products. Besides, immunosenescence, autoimmunity, endothelial cell damage, and decreased tissue regeneration could be the results of premature telomere erosion in patients with SLE. Herein, the molecular and cellular bases of inflammaging and cardiovascular complications in SLE patients will be extensively reviewed from the aspects of mitochondrial dysfunctions, abnormal bioenergetics/immunometabolism, and telomere/telomerase disequilibrium.

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Section: Mitochondrial Dysfunction Is One Of the Crucial Up-streammentioning

confidence: 99%

Molecular and Cellular Bases of Immunosenescence, Inflammation, and Cardiovascular Complications Mimicking “Inflammaging” in Patients with Systemic Lupus Erythematosus

Tsai

Shen

Liao

et al. 2019

IJMS

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“…This study linked mir-150-5p with intracellular MAVS protein expression. The MAVS protein levels were significantly higher in patients with lupus than in normal controls and were negatively correlated with lupus activity in our previous study [ 30 ]. The dynamic changes of mir-150-5p relating to lupus activity are worthy of further investigation.…”

Section: Discussionmentioning

confidence: 85%

“…This observation suggests the activation of the extrinsic apoptotic caspase-10-related pathway in SLE [ 22 , 39 ] and that caspase-10 is influenced by microRNA, which could be reflected by plasma microRNA levels in this study. Furthermore, we previously demonstrated that caspase-10 positively correlates with pIRF7, and caspase-9 and caspase-10 both positively correlate with each other, pIRF7, and MAVS 70 kD [ 30 ], indicating that interferons are links to cellular apoptosis and anti-virus immunity in SLE [ 16 , 40 – 42 ]. The pathways of MAVS and caspase-10 were examined by detecting plasma microRNA in SLE ( Figure 2 ).…”

Section: Discussionmentioning

confidence: 99%

“…Peripheral blood mononuclear cell (PBMC) intracellular protein levels of phosphorylated interferon regulator factor 7 (pIRF7), mitochondrial antiviral signaling protein (MAVS), and melanoma differentiation-associated protein 5 (MDA5) were detected by western blotting. Detailed procedures were described in the previous study [ 30 ]. The reagents and antibodies were rabbit polyclonal antibodies recognizing caspase-9 (Cell Signaling, #9501), phospho-IRF-7 (Cell signaling, #5184), rat polyclonal antibodies recognizing caspase-10 (Biolegend, #645202), and anti-mitochondrial antiviral signaling antibody (MAVS) (Abcam #ab25084).…”

Section: Methodsmentioning

confidence: 99%

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Investigation of MicroRNA in Mitochondrial Apoptotic Pathway in Systemic Lupus Erythematosus

Tsai

Kung

et al. 2018

BioMed Research International

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Background Accumulating evidence indicates that microRNAs play a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). This study tested the hypothesis that microRNA is associated with the mitochondrial apoptotic pathway in patients with SLE. Methods Thirteen patients were in the clinical comparison study and microRNA study and overall 19 patients in the study of intracellular protein. Levels of microRNAs were determined by miRNeasy kit in 13 patients with SLE and 29 volunteer normal controls. Intracellular levels of caspase-9, caspase-10, MAVS, MDA5, and pIRF7 in mononuclear cells from 19 patiens and the SLE disease activity index (SLEDAI) were determined in all SLE patients. Correlation analyses were performed among microRNAs, intracellular adaptor proteins, and caspase levels and mean SLEDAI. Results The ΔCT, defined by test reading difference between the target and the internal control microRNA (miR-451a), of miR-21-5p, miR-150-5p, and miR221-3p were significantly higher in plasma from SLE patients than in normal controls. miR-150-5pΔCT was positively correlated with both CRP and SLEDAI value. miR-150-5pΔCT was negatively associated with MAVS 70 kD. Caspase-10 protein levels were negatively associated with plasma miR-22-3pΔCT and miR-21-5pΔCT levels. Conclusions Our study confirmed the hypothesis that these microRNAs were associated with the mitochondrial apoptotic pathway in SLE. miR-150-5pΔCT was positively associated with SLE disease activity and it was negatively correlated with MAVS 70 kD, which may facilitate viral survival and further enhance inflammation. On the other hand, miR-22-3pΔCT and miR-21-5pΔCT, were negatively correlated with caspase-10 levels, which may repress extrinsic apoptosis and increase cell survival.

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“…However, the literature also contains data that indicate quite the opposite. For instance, a negative correlation was found between caspase‐9 levels and disease activity in patients with systemic lupus erythematosus (SLE), an autoimmune disease, in a study conducted by Yu‐Jih Su et al Rastin et al conducted a case‐control study investigating T lymphocyte apoptosis in 35 patients with SLE and found that caspase‐8 and caspase‐9 levels were lower in female patients as compared to the control group . As it is also apparent here, especially the caspase family has a role in inflammatory diseases.…”

Section: Discussionmentioning

confidence: 99%

Low levels of pannexin‐1 in Behçet’s syndrome

et al. 2019

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Objective Behçet's syndrome (BS) is a chronic, multisystemic and inflammatory syndrome. In our study, we aimed to compare the initiator, effector and inflammatory caspases and pannexin channel protein, which is thought to have an activity in inflammation, in the inflammatory process of BS, with healthy subjects, to investigate their level in patients and their relationship with the clinical findings. Method Forty‐six patients who were under follow‐up for BS in the Sivas Cumhuriyet University Medical Faculty Department of Internal Diseases, Rheumatology Unit, between January 2017 and June 2017 and 44 healthy controls (HC) who did not have any rheumatic, systemic or metabolic diseases, were enrolled in this study. Results The mean serum pannexin‐1 level was 6.36 (4.21‐527.2) pg/mL in the BS group and 255.8 (5.38‐2000) pg/mL in the HC group. Serum pannexin‐1 levels were statistically significantly lower in the BS group (P < 0.0001). The measured mean serum caspase‐3 level was 12.04 (11.25‐43.69) pg/mL in the group with BS and 12.1 (11.19‐484.3) pg/mL in the HC group (P = 0.143), mean serum caspase‐9 level was 22 (5.14‐29.33) pg/mL in the BS group and 22.01 (11.23‐850) pg/mL in the HC group (P = 0.593), mean serum caspase‐14 level was 6 (5.2‐8.21) pg/mL in the BS group and 6.15 (5.7‐353) pg/mL in the HC group (P = 0.053). Conclusion Comparison of serum caspase‐3, caspase‐9 and caspase‐14 levels in subjects with BS and in the HC group did not reveal any statistically significant differences. On the other hand, serum pannexin‐1 levels were statistically significantly lower in the BS group.

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Investigation of the caspase-dependent mitochondrial apoptotic pathway in mononuclear cells of patients with systemic lupus erythematosus

Cited by 15 publications

References 41 publications

Molecular and Cellular Bases of Immunosenescence, Inflammation, and Cardiovascular Complications Mimicking “Inflammaging” in Patients with Systemic Lupus Erythematosus

Molecular and Cellular Bases of Immunosenescence, Inflammation, and Cardiovascular Complications Mimicking “Inflammaging” in Patients with Systemic Lupus Erythematosus

Investigation of MicroRNA in Mitochondrial Apoptotic Pathway in Systemic Lupus Erythematosus

Low levels of pannexin‐1 in Behçet’s syndrome

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