in silico identification of protein-protein interactions in Silkworm,Bombyx mori

The Domesticated silkworm, Bombyx mori, an economically important insect has been used as a lepidopteran molecular model next only to Drosophila. Compared to the genomic information in silkworm, the protein-protein interaction data are limited. Therefore experimentally identified PPI maps from five model organisms such as E.coli, C.elegans, D.melanogaster, H. sapiens, S. cerevisiae were used to infer the PPI network of silkworm using the well-recognized Interlog based method. Among the 14623 silkworm proteins, 7736 protein-protein interaction pairs were predicted which include 2700 unique proteins of the silkworms. Using the iPfam interaction domains and the gene expression data, these predictions were validated. In that 625 PPI pairs of predicted network were associated with the iPfam domain-domain interactions and the random network has average of 9. In the gene expression method, the average PCC value of the predicted network and random network was 0.29 and 0.23100±0.00042 respectively. It reveals that the predicted PPI networks of silkworm are highly significant and reliable. This is the first PPI network for the silkworm which will provide a framework for deciphering the cellular processes governing key metabolic pathways in the silkworm, Bombyx mori and available at SilkPPI (http://210.212.197.30/SilkPPI/).     

Lupeol ameliorates aflatoxin B1-induced peroxidative hepatic damage in rats

Aflatoxins are potent hepatotoxic and hepatocarcinogenic agents. Reactive oxygen species and consequent peroxidative damage caused by aflatoxin are considered to be the main mechanisms leading to hepatotoxicity. The present investigation aims at assessing the hepatoprotective effect of lupeol, a pentacyclic triterpene isolated from the stem bark of Crataeva nurvala, on aflatoxin B(1) (AFB(1))-induced hepatotoxicity in a rat model. The hepatoprotection of lupeol is compared with silymarin, a well known standard hepatoprotectant. Lactate dehydrogenase, alkaline phosphatase, alanine and aspartate aminotransferases were found to be significantly increased in the serum and decreased in the liver of AFB(1) administered (1 mg/kg body mass, orally) rats, suggesting hepatic damage. Marked increase in the lipid peroxide levels and a concomitant decrease in the enzymic (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and glutathione-S-transferase) and nonenzymic (reduced glutathione, vitamin C and vitamin E) antioxidants in the hepatic tissue were observed in AFB(1) administered rats. Pretreatment with lupeol (100 mg/kg body mass, orally) and silymarin (100 mg/kg body mass, orally) for 7 days reverted the condition to near normalcy. Hepatoprotection by lupeol is further substantiated by the normal histologic findings as against degenerative changes in the AFB(1) administered rats. The results of this study indicate that lupeol is a potent hepatoprotectant as silymarin.     

Elevated mitochondrial activity distinguishes fibrogenic hepatic stellate cells and sensitizes for selective inhibition by mitotropic doxorubicin

Activation of hepatic stellate cells (HSCs) is an integral component of the wound‐healing process in liver injury/inflammation. However, uncontrolled activation of HSCs leads to constant secretion of collagen‐rich extracellular matrix (ECM) proteins, resulting in liver fibrosis. The enhanced ECM synthesis/secretion demands an uninterrupted supply of intracellular energy; however, there is a paucity of data on the bioenergetics, particularly the mitochondrial (mito) metabolism of fibrogenic HSCs. Here, using human and rat HSCs in vitro, we show that the mito‐respiration, mito‐membrane potential (Δψm) and cellular ‘bioenergetic signature’ distinguish fibrogenic HSCs from normal, less‐active HSCs. Ex vivo, HSCs from mouse and rat models of liver fibrosis further confirmed the altered ‘bioenergetic signature’ of fibrogenic HSCs. Importantly, the distinctive elevation in mito‐Δψm sensitized fibrogenic HSCs for selective inhibition by mitotropic doxorubicin while normal, less‐active HSCs and healthy human primary hepatocytes remained minimally affected if not, unaffected. Thus, the increased mito‐Δψm may provide an opportunity to selectively target fibrogenic HSCs in liver fibrosis.