CALR
Calreticulin precursor (CRP55) (Calregulin) (Endoplasmic reticulum resident protein 60) (ERp60) (HACBP) (grp60) [CRTC]
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Preeclampsia (PE) is a serious complication of human pregnancy. Women who have had PE, especially early-onset PE (EPE), have an increased risk of cardiovascular disease (CVD) later in life. However, how PE is linked to CVD is not well understood. We previously reported that HtrA4, a placenta-specific protease, is significantly elevated in EPE, and inhibits the proliferation of endothelial cells as well as endothelial progenitor cells (EPCs). This can potentially impair endothelial repair and regeneration, leading to endothelial aging, which is a major risk factor of CVD. In this study, we examined whether HtrA4 can alter endothelial expression of senescence genes. Human umbilical vein endothelial cells (HUVECs) and primary EPCs isolated from cord blood of healthy pregnancies were used as in vitro models. Firstly, HUVECs were treated with HtrA4 at the highest levels detected in EPE for 48h and screened with a senescence PCR array. The results were then validated by RT-PCR and ELISA in HUVECs and EPCs treated with HtrA4 for 24 and 48h. We observed that HtrA4 significantly up-regulated IGFBP3, SERPINE1 and SERPINB2, which all promote senescence. IGFBP-3 protein was also significantly elevated in the media of HtrA4-treated HUVECs. Conversely, a number of genes including CDKN2C, PCNA, CALR, CHEK2 and NOX4 were downregulated by HtrA4. Many of these genes also showed a similar trend of change in EPCs following HtrA4 treatment. Elevation of placenta-derived HtrA4 in PE alters the expression of endothelial genes to promote cellular senescence and may contribute to premature endothelial aging.
Keywords
- Endothelial aging
- Endothelial cells
- HtrA4
- Preeclampsia
- Senescence
The myeloproliferative neoplasms polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) display distinct clinical and pathologic features but are characterized by mutations in JAK2, MPL, and CALR leading to activation of the JAK-STAT pathway. This review addresses the pathogenesis and mechanisms of these mutant alleles and the unique interactions of both of age and gender.
MeSH Terms
- Age Factors
- Aging
- Alleles
- Female
- Hematologic Neoplasms
- Humans
- Janus Kinase 2
- Male
- Mutation
- Myeloproliferative Disorders
- Receptors, Thrombopoietin
- Sex Characteristics
- Sex Factors
Keywords
- Aging
- JAK2
- Myeloproliferative neoplasms
- Pathogenesis
- Sex differences
Maternal deprivation (MD) is a well-established protocol used to investigate neurobiological changes that are associated with the etiology of and vulnerability to stress-related diseases in animal models. The resulting psychophysiological effects, the timing and duration of these adverse stimuli, and the method by which they exert their effects on the animals remain unclear. This study characterized differences in the hippocampal expression of glucocorticoid receptors (GRs) and the calcium-binding proteins calretinin (CALR) and calbindin-D28k (CALB) in male and female rats that underwent different MD paradigms during the stress hyporesponsive period (SHRP). Both GRs and the two calcium-binding proteins were much more abundant in females than in males. MD paradigms had a significant effect on CALR and CALB expression in both males and females but affected GR levels only in males. Additionally, expression of the two calcium-binding proteins in the hippocampus responded differently to MD-induced stress, especially in females. Taken together, these results indicate that females are able to modulate their response to stress better than males.
MeSH Terms
- Aging
- Animals
- Calbindin 1
- Calbindin 2
- Calbindins
- Disease Models, Animal
- Female
- Hippocampus
- Male
- Maternal Deprivation
- Pregnancy
- Rats
- Rats, Sprague-Dawley
- Receptors, Glucocorticoid
- S100 Calcium Binding Protein G
- Sex Characteristics
- Stress, Psychological