Antinuclear antibodies recognize cellular autoantigens driven by apoptosis

Ramírez-Sandoval, Roxana; Sánchez-Rodríguez, Sergio Hugo; Oostdam, David Herrera-van; Avalos‐Díaz, Esperanza; Herrera‐Esparza, Rafael

doi:10.1016/s1297-319x(03)00019-8

Cited by 24 publications

(18 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The protein has an important role in assembly of kinetochore structure. In apoptotic cells, the protein is characterized as autoantigen that is cleaved to 60-kDa fragment and observed in blebs (27). It implies that ASRs may reduce autoimmune response in apoptotic phase.…”

Section: Discussionmentioning

confidence: 99%

Novel functional small RNAs are selectively loaded onto mammalian Ago1

Yamakawa¹,

Okuyama²,

Ogata³

et al. 2014

Nucleic Acids Research

View full text Add to dashboard Cite

Argonaute (Ago) proteins function in RNA silencing as components of the RNA-induced silencing complex (RISC). In lower organisms, the small interfering RNA and miRNA pathways diverge due in part to sorting mechanisms that direct distinct small RNA (sRNA) duplexes onto specific Ago-RISCs. However, such sorting mechanisms appear to be lost in mammals. miRNAs appear not to distinguish among Ago1–4. To determine the effect of viral infection on the sorting system, we compared the content of deep-sequenced RNA extracted from immunoprecipitation experiments with the Ago1 and Ago2 proteins using Epstein–Barr virus (EBV)-infected cells. Consistent with previous observations, sequence tags derived from miRNA loci in EBV and humans globally associate in approximately equivalent amounts with Ago1 and Ago2. Interestingly, additional sRNAs, which have not been registered as miRNAs, were associated with Ago1. Among them, some unique sequence tags derived from tandem loci in the human genome associate exclusively with Ago1 but not, or rarely, with Ago2. This is supported by the observation that the expression of the unique sRNAs in the cells is highly dependent on Ago1 proteins. When we knocked down Ago1, the expression of the Ago1-specific sRNAs decreased dramatically. Most importantly, the Ago1-specific sRNAs bound to mRNAs and regulated target genes and were dramatically upregulated, depending on the EBV life cycle. Therefore, even in mammals, the sorting mechanism in the Ago1–4 family is functional. Moreover, the existence of Ago1-specific sRNAs implies vital roles in some aspects of mammalian biology.

show abstract

Section: Discussionmentioning

confidence: 99%

Novel functional small RNAs are selectively loaded onto mammalian Ago1

Yamakawa¹,

Okuyama²,

Ogata³

et al. 2014

Nucleic Acids Research

View full text Add to dashboard Cite

show abstract

“…In lupus sun exposure induces apoptosis and would contribute to the pathogenesis of skin lesions in patients with cutaneous lupus phenotype (Kelly et al 2006;Kuhn et al 2006). The release of intact or modified intracellular ribonucleoproteins including Ro60 (Ramirez-Sandoval et al 2003) promotes the dendritic cell maturation and the production of interferon, that is critical in autoantibody production Positive ANA of the same patient. 6.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis and Redistribution of the Ro Autoantigen in Balb/c Mouse Like in Subacute Cutaneous Lupus Erythematosus

Herrera‐Esparza

Villalobos

Bollain-y-Goytia

et al. 2006

Journal of Immunology Research

Self Cite

View full text Add to dashboard Cite

In subacute cutaneous lupus eryhematosus (SCLE) the cutaneous antigens constitute the main source of Ro and La autoantigens. The aim of this investigation was to demonstrate if UV light increases the availability of Ro autoantigen in the skin, also the blocking effect of Ac-DEVD-CMK a caspase inhibitor was assessed. For this purpose newborn Balb/c mice were UVB irradiated (5–30 mJ/cm2) equivalent to a moderate to severe sunburn. Animals were injected with monoclonal anti-Ro antibodies from SCLE patients. Apoptosis was also induced by anti-Fas antibody injection. Skin samples were examined by direct immunofluoresence, by TUNEL, and the expression of caspase 3 by RT-PCR. Major findings of present studies were: 1. UVB irradiation and anti-Fas induced apoptosis of keratinocytes. 2. Apoptosis redistribute the Ro antigen on cell surface and is better triggered by Ro antibody. 3. The caspase 3 inhibitor Ac-DEVD-CMK decreases the availability of Ro autoantigen in epidermis and prevents deposition of anti-Ro. In conclusion, the caspase pathway would be blocked to avoid anti-Ro deposition along skin; this finding would be a prospect in the treatment of SCLE patients.

show abstract

“…The specific 70 kDa U1-snRNP protein is known as an autoantigenic protein for autoantibodies in serum from the patients with SLE or MCTD [26,27]. The specific 70 kDa U1-snRNP, cleaved during apoptosis by caspase 3 [23,24] and caspase 9 [28] and converted it into a C-terminally truncated 40 kDa protein fragment. High recognition of the 40-kd apoptotic fragment of U1-70 kDa has been shown to correlate with the presence of lupus-like skin disease in patients with antibodies against 70 kDa U1-snRNP [29,39,40].…”

Section: Discussionmentioning

confidence: 99%

“…The U1-snRNP complex is a common target for autoantibodies in serum of patients with SLE or mixed connective tissue disease (MCTD) [26,27]. Previous studies have demonstrated a specific cleavage of the 70-kDa protein component of the U1-snRNP by caspase 3 and caspase 9, which is recognized as a biochemical feature of apoptotic cell death [23,24,28]. The cleaved 70-kDa U1-snRNP will be converted into a C-terminally truncated 40-kDa protein fragment.…”

Section: Introductionmentioning

confidence: 99%

Human parvovirus B19 nonstructural protein NS1 enhanced the expression of cleavage of 70 kDa U1-snRNP autoantigen

et al. 2010

View full text Add to dashboard Cite

BackgroundHuman parvovirus B19 (B19) is known to induce apoptosis that has been associated with a variety of autoimmune disorders. Although we have previously reported that B19 non-structural protein (NS1) induces mitochondrial-dependent apoptosis in COS-7 cells, the precise mechanism of B19-NS1 in developing autoimmunity is still obscure.MethodsTo further examine the effect of B19-NS1 in presence of autoantigens, COS-7 cells were transfected with pEGFP, pEGFP-B19-NS1 and pEGFP-NS1K334E, a mutant form of B19-NS1, and detected the expressions of autoantigens by various autoantibodies against Sm, U1 small nuclear ribonucleoprotein (U1-snRNP), SSA/Ro, SSB/La, Scl-70, Jo-1, Ku, and centromere protein (CENP) A/B by using Immunoblotting.ResultsSignificantly increased apoptosis was detected in COS-7 cells transfected with pEGFP-B19-NS1 compared to those transfected with pEGFP. Meanwhile, the apoptotic 70 kDa U1-snRNP protein in COS-7 cells transfected with pEGFP-B19-NS1 is cleaved by caspase-3 and converted into a specific 40 kDa product, which were recognized by anti-U1-snRNP autoantibody. In contrast, significantly decreased apoptosis and cleaved 40 kDa product were observed in COS-7 cells transfected with pEGFP-NS1K334E compared to those transfected with pEGFP-B19-NS1.ConclusionsThese findings suggested crucial association of B19-NS1 in development of autoimmunity by inducing apoptosis and specific cleavage of 70 kDa U1-snRNP.

show abstract

Antinuclear antibodies recognize cellular autoantigens driven by apoptosis

Cited by 24 publications

References 32 publications

Novel functional small RNAs are selectively loaded onto mammalian Ago1

Novel functional small RNAs are selectively loaded onto mammalian Ago1

Apoptosis and Redistribution of the Ro Autoantigen in Balb/c Mouse Like in Subacute Cutaneous Lupus Erythematosus

Human parvovirus B19 nonstructural protein NS1 enhanced the expression of cleavage of 70 kDa U1-snRNP autoantigen

Contact Info

Product

Resources

About