The documentation of lead toxicity (plumbism) dates back to the times when man learnt its various applications. This versatile heavy metal is non-degradable and its ability to get accumulated in the body that goes undiagnosed, makes it a serious environmental health hazard. Lead is now known to affect almost every organ/tissue of the human body. With irreversible effects on neurobiological development of young children and foetus, its toxicity has lasting implications on the human life. Outlining the symptoms, diagnosis and treatment therapy for lead poisoning, the present review elaborates the pathophysiological effects of lead on various organs. This will be of immense help to the health professionals so as to inculcate a better understanding of the lead poisoning which otherwise is asymptomatic. With chelation therapy being the classic path of treatment, new strategies are being explored as additive/adjunct therapy. It is now understood that lead toxicity is completely preventable. In this regard significant efforts are in place in the developed countries whereas much needs to be done in the developing countries. Spreading the awareness amongst the masses by educating them and reducing the usage of lead following stricter industry norms appears to be the only roadmap to prevent lead poisoning. Efforts being undertaken by the Government of India and other organisations are also mentioned.
Background Lectins have come a long way from being identified as proteins that agglutinate cells to promising therapeutic agents in modern medicine. Through their specific binding property, they have proven to be anti-cancer, anti-insect, anti-viral agents without affecting the non-target cells. The Arisaema tortuosum lectin (ATL) is a known anti-insect and anti-cancer candidate, also has interesting physical properties. In the present work, its carbohydrate binding behavior is investigated in detail, along with its anti-proliferative property. Results The microcalorimetry of ATL with a complex glycoprotein asialofetuin demonstrated trivalency contributed by multiple binding sites and enthalpically driven spontaneous association. The complex sugar specificity of ATL towards multiple sugars was also demonstrated in glycan array analysis in which the trimannosyl pentasaccharide core N -glycan [Manα1-6(Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAcβ] was the highest binding motif. The high binding glycans for ATL were high mannans, complex N -glycans, core fucosylated N -glycans and glycans with terminal lactosamine units attached to pentasaccharide core. ATL induced cell death in IMR-32 cells was observed as time dependent loss in cell number, formation of apoptotic bodies and DNA damage. As a first report of molecular cloning of ATL, the in silico analysis of its cDNA revealed ATL to be a β -sheet rich heterotetramer. A homology model of ATL showed beta prism architecture in each monomer with 85% residues in favoured region of Ramachandran plot. Conclusions Detailed exploration of carbohydrate binding behavior indicated ATL specificity towards complex glycans, while no binding to simple sugars, including mannose. Sequence analysis of ATL cDNA revealed that during the tandem evolutionary events, domain duplication and mutations lead to the loss of mannose specificity, acquiring of new sugar specificity towards complex sugars. It also resulted in the formation of a two-domain single chain polypeptide with both domains having different binding sites due to mutations within the consensus carbohydrate recognition sites [QXDXNXVXY]. This unique sugar specificity can account for its significant biological properties. Overall finding of present work signifies anti-cancer, anti-insect and anti-viral potential of ATL making it an interesting molecule for future research and/or theragnostic applications. Electronic supplementary material The online version of this article (10.1186/s12867-019-0132-0) contains supplementary material, which is available to authorized users.
Solvent perturbation was used to study variations in structure of Arisaema helliborifolium lectin (AHL) with the help of circular dichroism (CD), intrinsic fluorescence (IF), extrinsic fluorescence, quenching and dynamic light scattering (DLS). AHL was studied under acidic, alkaline and 6 M guanidine hydrochloride (GuHCl) equilibrium states. Three structural states were identified for AHL at different conditions, that are native (N; pH 7.0), molten globule (MG; pH 2.0) and unfolded (U; pH 12.0). CD analysis revealed that 50% of secondary structure of AHL was β-sheet component. A complete loss of secondary structure was observed at GuHCl treatment. The tertiary structural changes as studied by changes in microenvironment of trp residues also suggested a pH induced MG state as in case of CD. Parameter-A analysis pointed at the multi-step unfolding process of lectin under varying pH (pH 1-13). A comparision of CD and IF data further indicated that different pathways were followed for secondary and tertiary structure unfolding. Tryptophans of native AHL were only partially exposed to solvent belonging to Class II. Hydrodynamic diameter (Dh ) measurements of AHL via DLS also confirmed of a pH induced molten globule. A thermally induced molten globule was identified for AHL between 54-60 °C as monitored by DLS. An irreversible thermal denaturation was observed with the formation of a large aggregate. The Dh of AHL at neutral pH was confirmed by transmission electron microscopy (TEM).
ABSTRACT-Aberrant glycosylation has been recognized as hallmark of cancer. Exploiting differences in glycosylation between malignant and healthy tissues offers excellent opportunities to identify sensitive and specific cancer biomarkers. Plant lectins have demonstrated the ability to specifically agglutinate malignant transformed cells. Lectins are sugar binding proteins or glycoprotein of non-immune origin which agglutinate cells or precipitate glycol-conjugates. Some lectins shown to the anti-proliferative effect on cancer cells. A wide scope of this application of lectins is that it can be used for diagnosis as well as therapeutics of cancer. The objective of the present study was to purify a lectin from tubers of Arisaema intermedium and evaluate in vitro anti-proliferative potential towards HCT-15, a human colon cancer cell line. The present study was conceived as an offshoot to the ongoing work on lectins in our laboratory. The already reported Arisaema intermedium (AIL) lectin was purified on asialofetuin linked amino-activated silica bead matrix. The purity of the affinity purified lectin was ascertained by SDS-PAGE, pH-8.3. The lectin activity was assessed by hemagglutination and protein concentration was determined by Lowry's method. The cytotoxicity of AIL towards HCT-15 was evaluated by MTT assay. The mechanism of anti-proliferative effect was assessed by evaluation of cell morphology, trypan blue exclusion assay, DNA fragmentation and nucleic acid content determination.
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