Proteasome Levels and Activity in Pregnancies Complicated by Severe Preeclampsia and Hemolysis, Elevated Liver Enzymes, and Thrombocytopenia (HELLP) Syndrome

Berryman, Kathryn; Buhimschi, Catalin S.; Zhao, Guomao; Axe, Michelle; Locke, Megan; Buhimschi, Irina A.

doi:10.1161/hypertensionaha.118.12437

Cited by 15 publications

(9 citation statements)

References 55 publications

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“…(Shang & Taylor, 2011). Plasma proteasome and immunoproteasome are significantly upregulated in PE and hemolysis, elevated liver enzymes, and thrombocytopenia syndrome (Berryman et al, 2019). Sun et al analyzed the gene expression profile of peripheral blood of patients with PE using gene microarray technology, and found that the expression of PSMC5 was increased (Sun et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Dissecting human trophoblast cell transcriptional heterogeneity in preeclampsia using single‐cell RNA sequencing

Zhang

Bian

Chen

et al. 2021

Molec Gen & Gen Med

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Objective PE is a pregnancy‐specific syndrome that affects 3%–5% of pregnant women. It often presents as new‐onset hypertension and proteinuria during the third trimester. PE progresses rapidly and may lead to serious complications, including the death of both mother and fetus. In low‐income countries, PE is one of the main causes of maternal and child mortality. While the cause of PE is still debated, clinical and pathological studies suggest that the placenta plays an important role in the pathogenesis of PE. Materials and Methods In this single‐cell RNA‐sequencing (RNA‐seq) study, the placenta was taken from the designated position after cesarean section. We compared placental cell subsets and their transcriptional heterogeneity between preeclampsia and healthy pregnancies using the single‐cell RNA‐seq technology. A developmental trajectory of human trophoblasts was shown. Results Gene expression in endoplasmic reticulum signaling pathways in syncytiotrophoblast was upregulated in the PE group. The villi cytotrophoblasts (VCT) and extravillous trophoblasts were mainly involved in immune responses. Conclusion The placental immune function of patients with PE was altered. Proteasomes, spliceosomes, ribosomes, and mitochondria were abnormally active in the new VCT cell type.

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Section: Discussionmentioning

confidence: 99%

Dissecting human trophoblast cell transcriptional heterogeneity in preeclampsia using single‐cell RNA sequencing

Zhang

Bian

Chen

et al. 2021

Molec Gen & Gen Med

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“…One example is the analysis of blood or bone-marrow derived samples of patients with multiple myeloma to determine response to treatment with approved proteasome inhibitors, and development of resistance [ 45 , 46 , 47 ]. Other studies analyzed blood plasma or bronchioalveolar lavage for an altered amount and activity of extracellular proteasomes as a potential biomarker for acute clinical conditions such as preeclampsia, burn injury, acute ischemic stroke, and acute respiratory stress syndrome [ 48 , 49 , 50 , 51 , 52 ]. Large scale population-based studies on intracellular proteasome activity in circulating lymphocytes, however, are missing.…”

Section: Introductionmentioning

confidence: 99%

Blood Immunoproteasome Activity Is Regulated by Sex, Age and in Chronic Inflammatory Diseases: A First Population-Based Study

Kammerl

Flexeder

Karrasch

et al. 2021

Cells

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Dysfunction of the immunoproteasome has been implicated in cardiovascular and pulmonary diseases. Its potential as a biomarker for predicting disease stages, however, has not been investigated so far and population-based analyses on the impact of sex and age are missing. We here analyzed the activity of all six catalytic sites of the proteasome in isolated peripheral blood mononuclear cells obtained from 873 study participants of the KORA FF4 study using activity-based probes. The activity of the immuno- and standard proteasome correlated clearly with elevated leukocyte counts of study participants. Unexpectedly, we observed a strong sex dimorphism for proteasome activity with significantly lower immunoproteasome activity in women. In aging, almost all catalytic activities of the proteasome were activated in aged women while maintained upon aging in men. We also noted distinct sex-related activation patterns of standard and immunoproteasome active sites in chronic inflammatory diseases such as diabetes, cardiovascular diseases, asthma, or chronic obstructive pulmonary disease as determined by multiple linear regression modeling. Our data thus provides a conceptual framework for future analysis of immunoproteasome function as a bio-marker for chronic inflammatory disease development and progression.

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“…Since the 20S proteasome is the only proteasome form found in blood [23], a small molecule ratio-based regulatory mechanism may be essential for the proteostasis of the entire organism. Indeed, changes in extracellular proteasome levels were observed during preeclampsia, cancer, and neurodegenerative diseases [24,25]. Interestingly, the role of ATP/Mg 2+ balance in the context of proteostasis maintenance might be supported by studies reporting decreased levels of Mg 2+ in the brain and cerebrospinal fluid associated with neurodegenerative diseases, including Alzheimer's and Parkinson diseases, as well as with aging [26,27].…”

Section: Resultsmentioning

confidence: 99%

The ATP/Mg2+ Balance Affects the Degradation of Short Fluorogenic Substrates by the 20S Proteasome

Morozov

Astakhova

Erokhov

et al. 2022

MPs

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Proteasomes hydrolyze most cellular proteins. The standard reaction to determine proteasome activity in cellular lysate or elsewhere contains AMC-conjugated peptide substrate, ATP, Mg2+, and DTT. ATP and Mg2+ are included to maintain 26S proteasome functionality. However, most cellular proteasomes are 20S proteasomes, and the effects of ATP on the turnover of fluorogenic substrates by 20S complexes are largely unknown. Here, we evaluated the effect of ATP alone or in combination with Mg2+ on the degradation of AMC-conjugated fluorogenic substrates by purified 20S proteasomes. Degradation of substrates used to determine chymotrypsin-, caspase- and trypsin-like proteasome activities was gradually decreased with the rise of ATP concentration from 0.25 to 10 mM. These effects were not associated with the blockage of the proteasome catalytic subunit active sites or unspecific alterations of AMC fluorescence by the ATP. However, ATP-induced peptide degradation slowdown was rescued by the addition of Mg2+. Moreover, the substrate degradation efficacy was proportional to the Mg2+/ATP ratio, being equal to control values when equimolar concentrations of the molecules were used. The obtained results indicate that when proteasome activity is assessed, the reciprocal effects of ATP and Mg2+ on the hydrolysis of AMC-conjugated fluorogenic substrates by the 20S proteasomes should be considered.

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Proteasome Levels and Activity in Pregnancies Complicated by Severe Preeclampsia and Hemolysis, Elevated Liver Enzymes, and Thrombocytopenia (HELLP) Syndrome

Cited by 15 publications

References 55 publications

Dissecting human trophoblast cell transcriptional heterogeneity in preeclampsia using single‐cell RNA sequencing

Dissecting human trophoblast cell transcriptional heterogeneity in preeclampsia using single‐cell RNA sequencing

Blood Immunoproteasome Activity Is Regulated by Sex, Age and in Chronic Inflammatory Diseases: A First Population-Based Study

The ATP/Mg2+ Balance Affects the Degradation of Short Fluorogenic Substrates by the 20S Proteasome

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