Cardiovascular diseases (CVDs) are a group of disorders affecting the heart and blood vessels and a leading cause of death worldwide. Thus, there is a need to identify new cardiokines that may protect the heart from damage as reported in GBD 2017 Causes of Death Collaborators (2018) (The Lancet 392:1736-1788). Follistatin-like 1 (FSTL1) is a cardiokine that is highly expressed in the heart and released to the serum after cardiac injury where it is associated with CVD and predicts poor outcome. The action of FSTL1 likely depends not only on the tissue source but also post-translation modifications that are target tissue- and cell-specific. Animal studies examining the effect of FSTL1 in various models of heart disease have exploded over the past 15 years and primarily report a protective effect spanning from inhibiting inflammation via transforming growth factor, preventing remodeling and fibrosis to promoting angiogenesis and hypertrophy. A better understanding of FSTL1 and its homologs is needed to determine whether this protein could be a useful novel biomarker to predict poor outcome and death and whether it has therapeutic potential. The aim of this review is to provide a comprehensive description of the literature for this family of proteins in order to better understand their role in normal physiology and CVD.
- MeSH
- biologické markery MeSH
- fibróza MeSH
- folistatin MeSH
- kardiovaskulární nemoci * MeSH
- lidé MeSH
- proteiny související s folistatinem * genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
N-methyl-D-aspartate receptors (NMDARs) belong to a family of ionotropic glutamate receptors that play essential roles in excitatory neurotransmission and synaptic plasticity in the mammalian central nervous system (CNS). Functional NMDARs consist of heterotetramers comprised of GluN1, GluN2A-D, and/or GluN3A-B subunits, each of which contains four membrane domains (M1 through M4), an intracellular C-terminal domain, a large extracellular N-terminal domain composed of the amino-terminal domain and the S1 segment of the ligand-binding domain (LBD), and an extracellular loop between M3 and M4, which contains the S2 segment of the LBD. Both the number and type of NMDARs expressed at the cell surface are regulated at several levels, including their translation and posttranslational maturation in the endoplasmic reticulum (ER), intracellular trafficking via the Golgi apparatus, lateral diffusion in the plasma membrane, and internalization and degradation. This review focuses on the roles played by the extracellular regions of GluN subunits in ER processing. Specifically, we discuss the presence of ER retention signals, the integrity of the LBD, and critical N-glycosylated sites and disulfide bridges within the NMDAR subunits, each of these steps must pass quality control in the ER in order to ensure that only correctly assembled NMDARs are released from the ER for subsequent processing and trafficking to the surface. Finally, we discuss the effect of pathogenic missense mutations within the extracellular domains of GluN subunits with respect to ER processing of NMDARs.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Follistatin-like 1 (FSTL1) is a secreted adipomyokine with a possible link to obesity; however, its connection to extreme obesity currently remains unknown. In order to analyze such association for the very first time, we employed a unique cohort of morbidly and super obese individuals with a mean BMI of 44.77 kg/m2 and measured the levels of circulating FSTL1. We explored the 3' UTR of FSTL1 to locate a genetic variant which impairs microRNA binding. We located and investigated such SNP (rs1057231) in relation to the FSTL1 protein level, obesity status, and other body composition parameters. We observed a significant decline in FSTL1 level in obese subjects in comparison to nonobese ones. The evaluated SNP was found to correlate with FSTL1 only in nonobese subjects. The presented results were not affected by sex since both males and females expressed FSTL1 equally. We suggest that the FSTL1 decrease observed in extremely obese subjects is a result of adipogenesis reduction accompanied by a senescence of preadipocytes which otherwise willingly express FSTL1, increased adipocyte apoptosis, and epigenetic FSTL1 silencing.
- MeSH
- 3' nepřekládaná oblast MeSH
- adipogeneze genetika MeSH
- běloši MeSH
- biologické markery krev MeSH
- dospělí MeSH
- down regulace MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA metabolismus MeSH
- mladiství MeSH
- morbidní obezita krev genetika MeSH
- obezita krev genetika MeSH
- proteiny související s folistatinem krev genetika MeSH
- senioři MeSH
- vazebná místa MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
