[Aberrant expression of arrestin-1 and recoverin in kidney tumors].

INTRODUCTION: Early diagnosis of renal cell carcinoma (RCC) is extremely difficult, due to the late development of clinical manifestations. The study of the aberrant expression of tumor-associated antigens and a production of autoantibodies to these proteins seems promising and novel method for RCC diagnosis. AIM: To evaluate the possibility of using arrestin-1 (Arr-1), recoverin (Rec) and autoantibodies against arrestin-1 (AAA1) and recoverin (AAR) as a kidney tumor biomarker. MATERIALS AND METHODS: Primary kidney tumors and metastases of 62 patients were investigated. For immunohistochemical studies, tissues were incubated with polyclonal antibodies against Rec and Arr1 as the main antibodies. Detection of AAR and AAA-1 in the serum of patients was performed using Western Blot analysis according to a standard protocol. RESULTS: Among 62 tumors, renal cell carcinoma (RCC) constitutes 50 cases (86.4%), and oncocytoma was diagnosed in 12 patients (19.4%). In 11 (22%) cases of RCC, distant metastases were detected. Positive expression of Rec was observed in almost 71% of all types of kidney tumors. In 61.3% of patients with RCC, Arr-1 expression was seen. In the serum, AAR was found only in 1 patient (1.6%) with RCC. However, unlike AAR, AAA-1 in the serum of patients was observed much more often (75.8%). CONCLUSION: According to our data, the presence of AAA1 in the serum, unlike AAR, can be considered as an early kidney tumor biomarker. The high expression of recoverin and arrestin-1 in kidney tumors suggests the use of these proteins in future as a marker for the diagnosis or even as a potential target for immunotherapy.

Beta-Arrestin1 Levels in Mononuclear Leukocytes Support Depression Scores for Women with Premenstrual Dysphoric Disorder.

Depression is very common in reproductive women particularly with premenstrual dysphoric disorder (PMDD), which is a severe form of premenstrual syndrome (PMS). Beta-arrestins were previously implicated in the pathophysiology, diagnosis and treatment for mood disorders. This study examined whether a measurement for beta-arrestin1 levels in peripheral blood mononuclear leukocytes (PBMC), could aid to distinguish between PMDD and PMS. Study participants (n = 25) were non-pregnant women between 18-42 years of age with the symptoms of PMS/PMDD, but not taking any antidepressants/therapy and at the luteal phase of menstruation. The levels of beta-arrestin1 protein in the PBMCs were determined by ELISA using human beta-arrestin1 kit. The beta-arrestin1 levels were compared with the Hamilton Depression Rating Scale scores among these women. The magnitude of the different parameters for Axis 1 mental disorders were significantly higher and beta arrestin1 protein levels in PBMCs were significantly lower in women with PMDD as compared to PMS women. The reduction in beta arrestin1 protein levels was significantly correlated with the severity of depressive symptoms. Beta-arrestin1 measurements in women may potentially serve for biochemical diagnostic purposes for PMDD and might be useful as evidence-based support for questionnaires.

[The clinical significance of ß-arrestin 2 expression in the serum of non-small cell lung cancer patients].

BACKGROUND AND OBJECTIVE: Non-small cell lung cancer (NSCLC) with high morbidity and mortality is the most common types of lung cancer. beta-arrestin 2 is a kind of soluble protein regulating signal transduction mediated by G protein coupling receptor. The aim of this research is to evaluate the clinical significance of ß-arrestin 2 expression in the serum of NSCLC patients. METHODS: The clinical and follow-up data of 20 healthy candidates and 67 patients diagnosed with NSCLC in Sun Yat-sen University Cancer Center from January 2005 to December 2006 was retrospectively analyzed. ELISA was applied to detect the expression of beta-arrestin 2. RESULTS: The serum level of ß-arrestin 2 in NSCLC patients were all Significantly lower than those in healthy controls (P<0.001, P<0.001, P<0.001). The serum level of ß-arrestin 2 in stage I NSCLC patients were higher than those in stage III as well as in stage IV (P<0.001, P<0.001). No statistical difference of ß-arrestin 2' serum level was found between with stage III and stage IV patients (P=0.273). Univariate prognostic factor analyzed by Kaplan-Meier method indicated patients' prognosis with high serum level of ß-arrestin 2 was better than patients with low and middle (P<0.001, P<0.001). The serum level of ß-arrestin 2 and the stage of NSCLC signally affected prognosis in COX regression model (P=0.003, P=0.004). CONCLUSION: The serum level of ß-arrestin 2 had significant difference between NSCLC patients and healthy controls, likewise between the early and advanced NSCLC patients. The serum level of ß-arrestin 2 affected NSCLC patients' prognosis.

Adrenal beta-arrestin 1 inhibition in vivo attenuates post-myocardial infarction progression to heart failure and adverse remodeling via reduction of circulating aldosterone levels.

OBJECTIVES: We investigated whether adrenal beta-arrestin 1 (ßarr1)-mediated aldosterone production plays any role in post-myocardial infarction (MI) heart failure (HF) progression. BACKGROUND: Heart failure represents 1 of the most significant health problems worldwide, and new and innovative treatments are needed. Aldosterone contributes significantly to HF progression after MI by accelerating adverse cardiac remodeling and ventricular dysfunction. It is produced by the adrenal cortex after angiotensin II activation of angiotensin II type 1 receptors (AT1Rs), G protein-coupled receptors that also signal independently of G proteins. The G protein-independent signaling is mediated by ßarr1 and ßarr2. We recently reported that adrenal ßarr1 promotes AT1R-dependent aldosterone production leading to elevated circulating aldosterone levels in vivo. METHODS: Adrenal-targeted, adenoviral-mediated gene delivery in vivo in 2-week post-MI rats, a time point around which circulating aldosterone significantly increases to accelerate HF progression, was performed to either increase the expression of adrenal ßarr1 or inhibit its function via expression of a ßarr1 C-terminal-derived peptide fragment. RESULTS: We found that adrenal ßarr1 overexpression promotes aldosterone elevation after MI, resulting in accelerated cardiac adverse remodeling and deterioration of ventricular function. Importantly, these detrimental effects of aldosterone are prevented when adrenal ßarr1 is inhibited in vivo, which markedly decreases circulating aldosterone after MI. Finally, the prototypic AT1R antagonist losartan seems unable to lower this adrenal ßarr1-driven aldosterone elevation. CONCLUSIONS: Adrenal ßarr1 inhibition, either directly or with AT1R "biased" antagonists that prevent receptor-ßarr1 coupling, might be of therapeutic value for curbing HF-exacerbating hyperaldosteronism.

[Beta-arrestin and NF-kappaB, AP-1 activity in peripheral blood mononuclear cells of guinea pigs sensitized by trichloroethylene].

OBJECTIVE: To explore the regulatory mechanism of immune response of guinea pigs sensitized by trichloroethylene (TCE), and the expression level of 3-arrestin, and the activity of NF-kappaB and AP-1 in peripheral blood mononuclear cells (PBMC) of guinea pigs sensitized by TCE. METHODS: Guinea pigs were treated with TCE based on the guinea pig maximum response test (GPMT); Blank control group and DNCB positive control group were established. Scores of skin reaction were evaluated and used to determine whether or not allergy in guinea pig. Then TCE treated group was divided into sensitized group or un-sensitized group. The expression levels of beta-arrestin protein, activity of NF-kappaB and AP-1 in PBMC were detected by Western Blotting and EMSA, respectively. TNF-alpha level in serum was detected by ELISA kits. RESULTS: No erythema or edema was found in the control group; part of guinea pigs treated with TCE developed erythema and edema, while obvious erythema and edema could be found in DNCB group. The sensitization rates were 71.4% and 100% in TCE and DNCB group, respectively. Compared with TCE un-sensitized group, expression of beta-arrestin and AP-1 activity were not significantly different in TCE sensitized group (P > 0.05). While the NF-kappaB activity was elevated obviously (P < 0.05). Compared with blank control groups [(32.118 +/- 12.550) pg/ml], serum TNF-alpha levels in TCE sensitized groups [(55.485 +/- 8.732) pg/ml] significantly elevated (P < 0.05); CONCLUSION: In guinea pigs, beta-arrestin and AP-1 may not be activated, while the NF-kappaB activation is significant, and plays a immune regulatory role in the immune reaction of allergy induced by TCE.

Beta-arrestin-1 levels: reduced in leukocytes of patients with depression and elevated by antidepressants in rat brain.

OBJECTIVE: Beta-arrestins play a pivotal role in G protein-coupled receptor desensitization. beta-Arrestins interfere in G protein receptor interaction, thus leading to desensitization of G protein-mediated receptor signaling. G protein receptor signaling and its desensitization were previously implicated in the pathophysiology of mood disorders and in the mechanism of action of antidepressant and mood-stabilizing treatments. The present study aims at quantitatively evaluating beta-arrestin-1 levels in leukocytes of patients with major depression and the effect of antidepressants on beta-arrestin-1 levels in rat brain. METHOD: Beta-arrestin-1 measurements were carried out in cortical, hippocampal, and striatal brain regions of rats chronically intragastrically treated with either imipramine, desipramine, or fluvoxamine. Similar measurements were conducted in mononuclear leukocytes of 36 untreated patients with major depression and 32 healthy volunteer subjects. Beta-arrestin-1 levels were evaluated through immunoblot analyses using monoclonal antibodies to beta-arrestin-1. RESULTS: Beta-arrestin-1 levels were significantly elevated by all three antidepressants in rat cortex and hippocampus, while in the striatum no alterations could be detected. This process became significant within 10 days and took 2-3 weeks to reach maximal increase. Mononuclear leukocytes of patients with depression showed significantly reduced immunoreactive quantities of beta-arrestin-1. The reduction in beta-arrestin-1 levels was significantly correlated with the severity of depressive symptoms. CONCLUSIONS: The findings in the rat study suggest beta-arrestin-1 elevation as a biochemical mechanism for antidepressant-induced receptor down-regulation. The findings in human subjects support the implication of beta-arrestin-1 in the pathophysiology of mood disorders. Beta-arrestin-1 measurements in patients with depression may potentially serve as a biochemical marker for depression.