Deltamethrin modulates the native structure of Hen Egg White Lysozyme and induces its aggregation at physiological pH.

Deltamethrin, a type II pyrethroid pesticide was initially considered as safe for human use. Recent studies have reported several pathophysiological effects of deltamethrin on human and non-human species. However, its effect on structure and function of protein leading to progressive neurodegeneration is poorly understood. In present study, we investigated the interaction of deltamethrin with Hen Egg White Lysozyme (HEWL) at physiological pH and tried to understand the effect of pesticide on structure and function of protein. Employing different biophysical techniques, we shown that deltamethrin induces in vitro aggregation of HEWL in concentration dependent manner. Interaction of pesticide with different amino acids, followed by exposure of hydrophobic regions was driving force of aggregation process. Apart from modulating the hydrophobic domain, deltamethrin is observed to reduce α-helical and promote ß-sheet content of lysozyme, eventually converting the globular protein into ThT sensitive amyloid fibrils and amorphous aggregates. Our study also indicate that deltamethrin induced aggregation reduces the catalytic activity of lysozyme.

Bacopa monnieri inhibit hen egg white lysozyme fibrillation and help in retaining its activity at acidic condition.

Inhibiting protein misfolding and aggregation is crucial for the treatment of several amyloidoses. Though various types of synthetic drugs are being explored as therapeutic agents, herbal extracts are better alternative owing to their natural origin, higher bioavailability and improved biosafety characteristics. In the present study, we demonstrate that night long (∼12 hr) preincubation of hen egg white lysozyme (HEWL) with Bacopa monnieri (brahmi) at neutral pH, impede the aggregation and fibrillation of protein at pH 2.0. Employing different biophysical techniques such as static and dynamic light scattering, Thioflavin T (ThT) assay, sedimentation assay and atomic force microscopy (AFM), we show that brahmi inhibit the HEWL aggregation in concentration dependent manner. 8-anilino-1-naphthalene sulfonate (ANS) fluorescence reveals that brahmi masks the exposure of hydrophobic domain of lysozyme. Significant recovery of enzymatic activity of HEWL in the presence of brahmi at pH 2.0 is salient feature of this work. Nearly 90% recovery of catalytic activity of lysozyme after 216 hr (9 days) of incubation indicate that interaction of HEWL-brahmi stabilizes the native structure of protein thus enhancing the activation energy barrier for protein misfolding and subsequent aggregation. Our findings show that brahmi could be promising alternative for the therapies of several protein misfolding disorders.Communicated by Ramaswamy H. Sarma.

A diagnostic test accuracy meta-analysis of maternal serum ischemia-modified albumin for detection of preeclampsia.

BACKGROUND/AIMS: Ischemia-modified albumin (IMA) has been widely accepted as a serological biomarker. IMA has been proposed as a simple and novel marker of oxidative stress in preeclampsia (PE). This systematic review and diagnostic test accuracy meta-analysis aims to evaluate the diagnostic accuracy of this novel serological biomarker, IMA to detect PE. METHODS: A systematic search of major databases was performed to identify all published diagnostic accuracy studies on IMA. Risk of bias and applicability concerns were assessed for included studies. Summary estimates; the pooled sensitivity, specificity, and the diagnostic odds ratio (DOR) of IMA for the diagnosis of PE were computed using random-effects models. The overall test performance was summarized using summary receiver operating characteristic (SROC) curve analysis. RESULTS: Six articles were included in this meta-analysis. The overall estimates of IMA in detecting PE were pooled sensitivity; 0.80 (95%CI 0.73-0.86), pooled specificity; 0.76 (95%CI 0.70-0.81), DOR; 14.32 (95%CI 5.06-40.57), and area under curve (AUC); 0.860. There was no between-study heterogeneity due to threshold effect. CONCLUSIONS: This meta-analysis showed IMA could be useful as a biomarker for PE with good accuracy (AUC = 0.860). However, further research is needed for re-evaluation and clinical validation of fairly promising results of this meta-analysis.

Maternal serum and fetal cord-blood ischemia-modified albumin concentrations in normal pregnancy and preeclampsia: a systematic review and meta-analysis.

BACKGROUND/AIMS: A meta-analysis of maternal serum ischemia-modified albumin (IMA) and fetal cord-blood IMA concentrations in normal pregnancy (NP) compared to non-pregnant healthy controls (HC) and in preeclampsia (PE) compared with normal pregnant controls were studied. METHODS: All major databases were searched for eligible studies. We included eight studies comparing serum IMA between NP and HC, 14 studies comparing serum IMA between PE and NP and five studies comparing cord-blood IMA between PE and NP groups. Meta-analyses on these included studies were performed using Review Manager 5.3. Pooled-overall effect size as standardized mean difference (SMD), publication bias, subgroup, and sensitivity analysis data were generated. RESULTS: Random-effects meta-analysis indicated a significant increase in serum IMA in the NP group (SMD = 0.98, p = .01) and the PE group (SMD = 0.94, p < .0001) as compared with HC and NP groups, respectively. And, the cord-blood IMA has been found to be significantly increased in PE (SMD = 6.51, p < .0001) compared with the NP group. CONCLUSIONS: This meta-analysis, the first of its kind showed that the increased serum IMA concentrations were indicative of increased oxidative stress in NP and PE. Measurement of maternal serum IMA and fetal cord-blood IMA concentrations were useful as simple, novel, and inexpensive markers of oxidative stress (OS) status in PE patients. Future large-scale studies are needed to explore IMA in relationship to the disease severity in PE.

Structural perturbation by arsenic triggers the aggregation of hen egg white lysozyme by promoting oligomers formation.

Arsenic trioxide is one of the most common metallic pollutants entering the food chain both by human activities and nature. Its entry inside the living organism through food, air and water results into the accumulation of heavy metal in several tissues which manifest several metabolic or hormonal disorders. Till now the effect of arsenic trioxide on protein misfolding and aggregation culminating into several neurodegenerative disorders is poorly understood. In the present study, we reveal the aggregation process of Hen Egg White Lysozyme (HEWL) in presence of arsenic trioxide (As2O3) at physiological conditions. We show that As2O3 promote the in vitro aggregation of HEWL in concentration dependent manner. Early phase of aggregation is observed to be induced by exposure of hydrophobic surfaces which later reorganized to promote further self-association leading to ß sheet structure. Presence of lower ordered oligomers after two days and higher ordered oligomers along with amorphous aggregates after week long incubation indicate that As2O3 drives the self-assembly of lysozyme towards oligomeric form.