Knockdown of Cytosolic Glutaredoxin 1 Leads to Loss of Mitochondrial Membrane Potential: Implication in Neurodegenerative Diseases

Mitochondrial dysfunction including that caused by oxidative stress has been implicated in the pathogenesis of neurodegenerative diseases. Glutaredoxin 1 (Grx1), a cytosolic thiol disulfide oxido-reductase, reduces glutathionylated proteins to protein thiols and helps maintain redox status of proteins during oxidative stress. Grx1 downregulation aggravates mitochondrial dysfunction in animal models of neurodegenerative diseases, such as Parkinson's and motor neuron disease. We examined the mechanism underlying the regulation of mitochondrial function by Grx1. Downregulation of Grx1 by shRNA results in loss of mitochondrial membrane potential (MMP), which is prevented by the thiol antioxidant, α-lipoic acid, or by cyclosporine A, an inhibitor of mitochondrial permeability transition. The thiol groups of voltage dependent anion channel (VDAC), an outer membrane protein in mitochondria but not adenosine nucleotide translocase (ANT), an inner membrane protein, are oxidized when Grx1 is downregulated. We then examined the effect of β-N-oxalyl amino-L-alanine (L-BOAA), an excitatory amino acid implicated in neurolathyrism (a type of motor neuron disease), that causes mitochondrial dysfunction. Exposure of cells to L-BOAA resulted in loss of MMP, which was prevented by overexpression of Grx1. Grx1 expression is regulated by estrogen in the CNS and treatment of SH-SY5Y cells with estrogen upregulated Grx1 and protected from L-BOAA mediated MMP loss. Our studies demonstrate that Grx1, a cytosolic oxido-reductase, helps maintain mitochondrial integrity and prevents MMP loss caused by oxidative insult. Further, downregulation of Grx1 leads to mitochondrial dysfunction through oxidative modification of the outer membrane protein, VDAC, providing support for the critical role of Grx1 in maintenance of MMP

A Review on Feasibility of Silkworm Pupal Meal in Livestock and Poultry

The rising cost of soy meal and other ingredients for animal and poultry feed has sparked a hunt for protein alternatives. Pupae of silkworms are a good source of protein and are included in the natural feed diet. Over the last decade, studies on the replacement of feedstuff with silkworm pupal have emerged with promising results. The silkworm pupae, which are a byproduct of the silk reeling industry, possess a high nutritional value which makes them a great choice for poultry feed. Dry pupae contain 50–70% crude protein and 24–33% crude lipid and is a high-quality insect protein source with a rich, balanced content of essential amino acids. Recommended inclusion levels of silkworm pupae meal have been developed as a result of several studies conducted on livestock species. This meal is guaranteed to provide better growth performance than commercial meal (soyabean meal)

Assessing the Impact of Abamectin and Diafenthiuron on Silkworm Larval Growth and Survival

An experiment was conducted primarily to evaluate chemicals exhibiting dual insecticidal and acaricidal properties, with a specific focus on their compatibility with silkworms and indigenous natural predators within the mulberry ecosystem, to evaluate abamectin 1.9% EC and diafenthiuron 50% WP for safety period on mulberry silkworm, Bombyx mori L. (Jan-Feb and Mar-April 2023) where in the pesticides were sprayed on mulberry at different durations, after spray were fed to the silkworms from third instar onwards. There was no mortality (0.00%) of silkworm observed in the treatments during two seasons and the larval progression 100% during third, fourth and fifth instars. The total larval duration was found shortest when the silkworms were fed with mulberry leaves harvested from the plots sprayed with abamectin 1.9% EC at 0.75ml/lit (22.30 and 23.22 days) and diafenthiuron 50% WP at 1 g/lit (22.77 and 23.07 days) at 15 and 21 DAS, respectively. The larval weight was significantly maximum in the treatments with abamectin 1.9% EC at 0.75 ml/lit (4.29 and 4.08 g/larvae) and diafenthiuron 50% WP at 1 g/lit (4.17 and 4.06 g/ larvae), respectively at 15 and 21 DAS. The Effective Rate of Rearing (ERR %) was found highest with diafenthiuron 50% WP at 1 g/lit (97.78 and 96.67 % at 15 and 21 DAS) and abamectin 1.9% EC at 0.75 ml/lit (97.78 and 96.67 % at 15 and 21 DAS) that was comparable with control. The molecules, diafenthiuron 50% WP at 1 g/lit and abamectin 1.9% EC at 0.75 ml/lit were found safer to silkworms at 15 and 21 DAS in terms of survival and larval growth

NRAGE, a p75NTR adaptor protein, is required for developmental apoptosis in vivo.

NRAGE (also known as Maged1, Dlxin) is a member of the MAGE gene family that may play a role in the neuronal apoptosis that is regulated by the p75 neurotrophin receptor (p75NTR). To test this hypothesis in vivo, we generated NRAGE knockout mice and found that NRAGE deletion caused a defect in developmental apoptosis of sympathetic neurons of the superior cervical ganglia, similar to that observed in p75NTR knockout mice. Primary sympathetic neurons derived from NRAGE knockout mice were resistant to apoptosis induced by brain-derived neurotrophic factor (BDNF), a pro-apoptotic p75NTR ligand, and NRAGE-deficient sympathetic neurons show attenuated BDNF-dependent JNK activation. Hair follicle catagen is an apoptosis-like process that is dependent on p75NTR signaling; we show that NRAGE and p75NTR show regulated co-expression in the hair follicle and that identical defects in hair follicle catagen are present in NRAGE and p75NTR knockout mice. Interestingly, NRAGE knockout mice have severe defects in motoneuron apoptosis that are not observed in p75NTR knockout animals, raising the possibility that NRAGE may facilitate apoptosis induced by receptors other than p75NTR. Together, these studies demonstrate that NRAGE plays an important role in apoptotic-signaling in vivo.Cell Death and Differentiation advance online publication, 5 September 2008; doi:10.1038/cdd.2008.127