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General Comment |
NCBI Summary:
This gene encodes the acidic form of complement factor 4, part of the classical activation pathway. The protein is expressed as a single chain precursor which is proteolytically cleaved into a trimer of alpha, beta, and gamma chains prior to secretion. The trimer provides a surface for interaction between the antigen-antibody complex and other complement components. The alpha chain may be cleaved to release C4 anaphylatoxin, a mediator of local inflammation. Deficiency of this protein is associated with systemic lupus erythematosus and type I diabetes mellitus. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. Varying haplotypes of this gene cluster exist, such that individuals may have 1, 2, or 3 copies of this gene.
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Comment |
Endocrine Society 2004
[P2-252] Involvement of Complement System in the Ovulation.
Giyoun Na, Mary C Gieske, CheMyong Ko, Yongbum Koo. Sch of Biotechnology and Biomed Sci, Inje Univ, Gimhae, Republic of Korea; Clin Scis, Univ of Kentucky, Lexington, KY
It is well known that the ovulation is an inflammatory-like process, which may involve the activation of complement system. Complement system is composed of various proteins that are sequentially activated by inflammatory signal resulting in the formation of membrane attack complex (MAC), which disrupts various types of cell membranes. At the site of inflammatory reaction, on the other hand, host cells produce regulators of complement systems which inhibit the MAC formation. In order to see whether complement system is involved in the ovulatory process, expression patterns of the membrane bound forms of regulators of complement activation (RCA) were examined in the periovulatory stage ovaries. For this purpose, a rat ovarian gene expression database (rOGED) was used. rOGED provides quantitative temporal mRNA expression profiles of 31,000 genes at ovarian (OVA), granulosa cell (GC), and non-granulosa/oocyte ovarian tissue (NGO) levels at various stages of follicular development (Abstract #852214). Of the three main types of RCAs, rOGED detected the expressions of mRNAs for membrane inhibitor of reactive lysis (CD59) and decay accelerating factor (DAF; CD55), but not membrane co-factor protein (MCP). CD59 mRNA was expressed both in GC and NGO all over the time points examined, with the peak expression at 12 h post treatment hCG. Expression of DAF mRNA was dramatically, yet transiently increased at 6 h post hCG treatment. Ten fold higher expression of DAF mRNA was detected in NGO than in GC at all time points examined. Northern blot analyses have confirmed the tissue- and time-dependent expression patterns of the rOGED data. We further examined the expression patterns of the various components of complement system. Surprisingly, within 6 hours of hCG treatment, two fold increase in mRNA expression was observed in the mRNAs for C1q , C3 and C4 proteins. Interestingly, those components were detected only in the NGO, except C1 that is expressed both in GC and NGO. The ovulatory inflammatory reaction is known to facilitate the process of follicle rupture. The inflammatory reaction, however, may give serious damages to the growing follicles, ovulated follicles and other important ovarian tissues. Present study strongly indicates that complement system may be involved in the ovulatory inflammation and the RCAs are expressed to protect ruptured follicles as well as other parts of the ovarian tissues from the potential attack by the complement system.
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Comment |
A Proteomic Analysis of Human Follicular Fluid: Comparison between Younger and Older Women with Normal FSH Levels. Hashemitabar M 2014 et al.
The follicular fluid (FF) is produced during folliculogenesis and contains a variety of proteins that play important roles in follicle development and oocyte maturation. Age-related infertility is usually considered as a problem that can be solved by assisted reproduction technology. Therefore, the identi?cation of novel biomarkers that are linked to reproductive aging is the subject of this study. FF was obtained from healthy younger (20-32 years old) and older (38-42 years old) women undergoing intracytoplasmic sperm injection (ICSI) due to male factor infertility. The FF was analyzed by two-dimensional gel electrophoresis (2-DE). The power of two-dimensional gel electrophoresis and the identi?cation of proteins were exploited using matrix-assisted laser desorption-ionization time-of-flight/time-of-flight (MALDI-TOF-TOF) mass spectrometry. Twenty three protein spots showed reproducible and significant changes in the aged compared to the young group. Of these, 19 protein spots could be identified using MALDI-TOF-TOF-MS. As a result of MASCOT search, five unique downregulated proteins were identified in the older group. These were identified as serotransferrin, hemopexin precursor, complement C3, C4 and kininogen. A number of protein markers were found that may help develop diagnostic methods of infertility.
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