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

Su YJ, Cheng TT, Chen CJ, Chang WN, Tsai NW, Kung CT, Wang HC, Lin WC, Huang CC, Chang YT, Su CM, Chiang YF, Cheng BC, Lin YJ, Lu CH - J Transl Med (2014)

Bottom Line: Disease activity was positively associated with the APO2.7 of CD19+ cells in SLE, but negatively associated with MAVS and caspase-9 levels (all p < 0.05).Markers of viral infection and anti-virus transcription factors like MDA5, MAVS, and pIRF7 were significantly higher in SLE patients than in disease controls (p < 0.05).The disease activity of SLE is positively associated with APO2.7 level of CD19+ cells but negatively associated with MAVS and caspase-9 levels, which all point to a mitochondrial pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, Taiwan. bensu8@gmail.com.

ABSTRACT

Background: This study aimed to explore the role of apoptosis initiators, caspase-9, caspase-10, mitochondrial anti-viral signaling protein (MAVS), and interferon regulatory factor 7 (pIRF7), in patients with systemic lupus erythematosus (SLE).

Methods: Leukocyte apoptosis was determined by flow cytometry, including annexin V, APO2.7, and 7-amino-actinomycin D (7-AAD) on each subtype of leukocyte in 35 patients with SLE, 15 disease controls, and 17 volunteer normal controls. Levels of caspase-9, caspase-10, MAVS, and pIRF7 in mononuclear cells and the disease activity index (SLEDAI) in the SLE patients were determined. Correlation among intracellular adaptor proteins and caspase levels were calculated.

Results: The SLE patients had higher APO2.7 in total leukocyte, lymphocyte, and monocytes, and higher late apoptosis markers in total leukocytes and neutrophils than normal controls (all p < 0.05). Disease activity was positively associated with the APO2.7 of CD19+ cells in SLE, but negatively associated with MAVS and caspase-9 levels (all p < 0.05). Markers of viral infection and anti-virus transcription factors like MDA5, MAVS, and pIRF7 were significantly higher in SLE patients than in disease controls (p < 0.05). Caspase-9 and caspase-10 levels positively correlated with MAVS and pIRF7 in SLE patients (p < 0.05).

Conclusions: The disease activity of SLE is positively associated with APO2.7 level of CD19+ cells but negatively associated with MAVS and caspase-9 levels, which all point to a mitochondrial pathway.

No MeSH data available.


Related in: MedlinePlus

Pathways of cell death and the interactions between initiator caspases. This figure is mainly from the reference Cell Death Differ, 2012. 19(1): p. 107-20.
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Fig1: Pathways of cell death and the interactions between initiator caspases. This figure is mainly from the reference Cell Death Differ, 2012. 19(1): p. 107-20.

Mentions: A recent study has demonstrated elevated apoptosis in SLE patients [2] and a correlation between disease activity and the apoptotic marker APO2.7 on CD19+ lymphocytes. Detection of APO2.7 apoptosis indicates that the inner side of the outer membrane of the mitochondria is turned over, which may be initiated by either an extrinsic or intrinsic apoptotic process [3]. The external apoptotic signal is executed through cell surface receptors (e.g. TNFR1, FAS), whereas caspase-10 is activated through proteolytic processes into several active isoforms (e.g. active cleaved form) [3]. Caspase-9 is known either as an initiator caspase of the mitochondrial intrinsic apoptotic pathway or an adaptor of the dependent receptor of apoptosis (Figure 1) [3,4].Figure 1


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

Su YJ, Cheng TT, Chen CJ, Chang WN, Tsai NW, Kung CT, Wang HC, Lin WC, Huang CC, Chang YT, Su CM, Chiang YF, Cheng BC, Lin YJ, Lu CH - J Transl Med (2014)

Pathways of cell death and the interactions between initiator caspases. This figure is mainly from the reference Cell Death Differ, 2012. 19(1): p. 107-20.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4226892&req=5

Fig1: Pathways of cell death and the interactions between initiator caspases. This figure is mainly from the reference Cell Death Differ, 2012. 19(1): p. 107-20.
Mentions: A recent study has demonstrated elevated apoptosis in SLE patients [2] and a correlation between disease activity and the apoptotic marker APO2.7 on CD19+ lymphocytes. Detection of APO2.7 apoptosis indicates that the inner side of the outer membrane of the mitochondria is turned over, which may be initiated by either an extrinsic or intrinsic apoptotic process [3]. The external apoptotic signal is executed through cell surface receptors (e.g. TNFR1, FAS), whereas caspase-10 is activated through proteolytic processes into several active isoforms (e.g. active cleaved form) [3]. Caspase-9 is known either as an initiator caspase of the mitochondrial intrinsic apoptotic pathway or an adaptor of the dependent receptor of apoptosis (Figure 1) [3,4].Figure 1

Bottom Line: Disease activity was positively associated with the APO2.7 of CD19+ cells in SLE, but negatively associated with MAVS and caspase-9 levels (all p < 0.05).Markers of viral infection and anti-virus transcription factors like MDA5, MAVS, and pIRF7 were significantly higher in SLE patients than in disease controls (p < 0.05).The disease activity of SLE is positively associated with APO2.7 level of CD19+ cells but negatively associated with MAVS and caspase-9 levels, which all point to a mitochondrial pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, Taiwan. bensu8@gmail.com.

ABSTRACT

Background: This study aimed to explore the role of apoptosis initiators, caspase-9, caspase-10, mitochondrial anti-viral signaling protein (MAVS), and interferon regulatory factor 7 (pIRF7), in patients with systemic lupus erythematosus (SLE).

Methods: Leukocyte apoptosis was determined by flow cytometry, including annexin V, APO2.7, and 7-amino-actinomycin D (7-AAD) on each subtype of leukocyte in 35 patients with SLE, 15 disease controls, and 17 volunteer normal controls. Levels of caspase-9, caspase-10, MAVS, and pIRF7 in mononuclear cells and the disease activity index (SLEDAI) in the SLE patients were determined. Correlation among intracellular adaptor proteins and caspase levels were calculated.

Results: The SLE patients had higher APO2.7 in total leukocyte, lymphocyte, and monocytes, and higher late apoptosis markers in total leukocytes and neutrophils than normal controls (all p < 0.05). Disease activity was positively associated with the APO2.7 of CD19+ cells in SLE, but negatively associated with MAVS and caspase-9 levels (all p < 0.05). Markers of viral infection and anti-virus transcription factors like MDA5, MAVS, and pIRF7 were significantly higher in SLE patients than in disease controls (p < 0.05). Caspase-9 and caspase-10 levels positively correlated with MAVS and pIRF7 in SLE patients (p < 0.05).

Conclusions: The disease activity of SLE is positively associated with APO2.7 level of CD19+ cells but negatively associated with MAVS and caspase-9 levels, which all point to a mitochondrial pathway.

No MeSH data available.


Related in: MedlinePlus