Tobacco use is associated with low peripheral beta-arrestin 1 levels in major depression: A preliminary report.

BACKGROUND: Understanding mechanisms associated with depressed smokers is a relevant question given that tobacco use disorder with comorbid major depressive disorder (MDD) has worse outcomes. The beta-arrestin 1 (ARRB1) pathway is a suggested biomarker for major depressive disorder and is involved in both antidepressant mechanism of action and tobacco addiction. We aimed to assess the association between smoking and peripheral ARRB1 expression in participants who exhibited MDD with current major depressive episode (MDE). BASIC PROCEDURES: 61 participants who exhibited MDD with current MDE with a score above 17 on the Hamilton Depression Rating Scale (HDRS), and who were free from antidepressant drug treatment for at least one month before inclusion, were assessed for tobacco use and cigarettes/day. Peripheral ARRB1 expression was assessed by sandwich ELISA from peripheral blood mononuclear cells (PBMC). FINDINGS: In participants who exhibited MDD with current MDE, peripheral ARRB1 expression was lower in tobacco users (n = 20, mean (SD) 4.795 (1.04) ng/mg of total protein) compared to non-tobacco users (n = 41, mean (SD) 6.19 (1.56) ng/mg; FDR p-value= 0.0044). Higher daily tobacco consumption was associated with lower peripheral ARRB1 expression (r = -0.314; FDR p-value=0.037). CONCLUSIONS: Tobacco consumption should be considered in studies of ARRB1 in participants who exhibit MDD. ARRB1 signaling is a new target of interest with a potential clinical implication for people with MDD and tobacco use disorder.

HSPA8 Is Identified as a Novel Regulator of Hypertensive Disorders in Pregnancy by Modulating the ß-Arrestin1/A1AR Axis.

Heat shock protein alpha 8 (HSPA8) was found to be downregulated in the placentas of patients with hypertensive disorders in pregnancy (HDP). We aim to explore the underlying role and mechanism of HSPA8 in HDP progression. Herein, HSPA8 mRNA expression in placentas and peripheral blood of patients with HDP and normal pregnant controls was measured with RT-qPCR. We found that HSPA8 expression was downregulated in placentas and peripheral blood of patients with HDP. HTR8/SVneo human trophoblast cells were transfected with pcDNA-HSPA8 or si-HSPA8. HSPA8 overexpression promoted cell proliferation, migration, and MMP-2 and MMP-9 protein levels, and inhibited apoptosis, while HSPA8 silencing showed the opposite results. Co-immunoprecipitation assay validated the binding between HSPA8 and ß-arrestin1, as well as ß-arrestin1 and A1AR proteins. HSPA8 bound with ß-arrestin1 protein and promoted ß-arrestin1 expression. ß-arrestin1 bound with A1AR protein and inhibited A1AR expression. Then, HTR8/SVneo cells were transfected with pcDNA-HSPA8 alone or together with si-ß-arrestin1, as well as transfected with pcDNA-ß-arrestin1 alone or together with pcDNA-A1AR. ß-arrestin1 silencing reversed the effects of HSPA8 overexpression on HTR8/SVneo cell functions. ß-arrestin1 overexpression promoted cell proliferation migration, and MMP-2 and MMP-9 protein levels, and inhibited apoptosis, while these effects were reversed by A1AR overexpression. Lentivirus HSPA8 overexpression vector (Lv-HSPA8) was injected into a preeclampsia (PE) rat model, which attenuated blood pressure and fetal detrimental changes in PE rats. In conclusion, HSPA8 promoted proliferation and migration and inhibited apoptosis in trophoblast cells, and attenuated the symptoms of PE rats by modulating the ß-arrestin1/A1AR axis. Our study provided a novel theoretical evidence and potential strategy for HDP treatment.

Do Progestin-Only Contraceptives Contribute to the Risk of Developing Depression as Implied by Beta-Arrestin 1 Levels in Leukocytes? A Pilot Study.

We reported previously that reduction in beta-arrestin 1 (ß-AR 1) protein levels in peripheral blood mononuclear leukocytes (PBMC) significantly correlated with the severity of depressive symptoms in reproductive women. In this pilot study, we used ß-AR 1 protein levels in PBMC as a marker for developing depressive symptoms and the Hamilton Depression Rating Scale (HAM-D) scores to assess potential mood-related side effects of oral contraceptive use for routine birth control among women. We evaluated 29 women in this study. We enrolled the participants in three groups: Estrogen-progestin combination-oral contraceptives (COC, n = 10), progestin-only contraceptives (POC, n = 12), and non-hormonal or no contraceptives (NC, n = 7). We determined the ß-AR 1 protein levels in PBMCs by enzyme-linked immunosorbent assay (ELISA). We found that women in the POC group had significantly higher HAM-D scores compared to those in the COC (p < 0.0004) and NC (p < 0.004). The levels of ß-AR 1 protein were significantly attenuated in women in the POC group compared to women in the NC group (p = 0.03). Our findings suggest that the use of POC is a potential risk factor for developing depressive symptoms.

Identification of beta-arrestin-1 as a diagnostic biomarker in lung cancer.

BACKGROUND: Distinguishing lung adenocarcinoma (ADC) from squamous cell carcinoma (SCC) has a tremendous therapeutic implication. Sometimes, the commonly used immunohistochemistry (IHC) markers fail to discriminate between them, urging for the identification of new diagnostic biomarkers. METHODS: We performed IHC on tissue microarrays from two cohorts of lung cancer patients to analyse the expression of beta-arrestin-1, beta-arrestin-2 and clinically used diagnostic markers in ADC and SCC samples. Logistic regression models were applied for tumour subtype prediction. Parallel reaction monitoring (PRM)-based mass spectrometry was used to quantify beta-arrestin-1 in plasma from cancer patients and healthy donors. RESULTS: Beta-arrestin-1 expression was significantly higher in ADC versus SCC samples. Beta-arrestin-1 displayed high sensitivity, specificity and negative predictive value. Its usefulness in an IHC panel was also shown. Plasma beta-arrestin-1 levels were considerably higher in lung cancer patients than in healthy donors and were higher in patients who later experienced a progressive disease than in patients showing complete/partial response following EGFR inhibitor therapy. CONCLUSIONS: Our data identify beta-arrestin-1 as a diagnostic marker to differentiate ADC from SCC and indicate its potential as a plasma biomarker for non-invasive diagnosis of lung cancer. Its utility to predict response to EGFR inhibitors is yet to be confirmed.