Genetic modulators associated with regulatory surveillance of mitochondrial quality control, play a key role in regulating stress pathways and longevity in C. elegans

Sarkar, Arunabh; Hameed, Rohil; Mishra, Anjali; Bhatta, Rabi Sankar; Nazir, Aamir

doi:10.1016/j.lfs.2021.120226

Cited by 10 publications

(8 citation statements)

References 77 publications

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“…C. elegans strains were cultured on nematode growth media having lawns of E. coli OP-50 strain bacteria that were incubated at 22 °C [ 11 ]. Synchronized worms were obtained by treating gravid adult-stage worms with an axenising solution (4% sodium hypochlorite solution) followed by washings using M9 buffer.…”

Section: Methodsmentioning

confidence: 99%

“…The commonly used vector for this includes L4440, thus, when the worm feeds on bacteria having plasmid/clone of interest gets into C. elegans system and interacts with the gene of interest and silences it via RNAi phenomenon. For this study, the RNAi clones were grown independently, in LB medium having 50 μg/ml ampicillin, followed by incubation for 6–8 h at 37 °C, [ 11 ]. Bacterial clones were seeded onto NGM plates having 5 mM-IPTG (isopropylthio-beta- d -galactoside), which is used for the siRNA induction with carbenicillin (25 mg/l).…”

Section: Methodsmentioning

confidence: 99%

“…The pattern of thrashing in C. elegans gives a measure of its healthy muscular and neurobehavioral function, hence the thrashing rate was studied, which directly reveals the amount of dopamine accessible in the worms under different genetic manipulations and test conditions [ 11 ]. Worms were reared on RNAi-treated plates for 48 h in this test, since the RNAi treatment via oral administration is done at embryo stage and it requires 48 h to reach the stage being studied, that is L4/YA stage.…”

Section: Methodsmentioning

confidence: 99%

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Functional implications of NHR-210 enrichment in C. elegans cephalic sheath glia: insights into metabolic and mitochondrial disruptions in Parkinson's disease models

Hameed,

Naseer,

Saxena

et al. 2024

Cell. Mol. Life Sci.

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Glial cells constitute nearly half of the mammalian nervous system's cellular composition. The glia in C. elegans perform majority of tasks comparable to those conducted by their mammalian equivalents. The cephalic sheath (CEPsh) glia, which are known to be the counterparts of mammalian astrocytes, are enriched with two nuclear hormone receptors (NHRs)—NHR-210 and NHR-231. This unique enrichment makes the CEPsh glia and these NHRs intriguing subjects of study concerning neuronal health. We endeavored to assess the role of these NHRs in neurodegenerative diseases and related functional processes, using transgenic C. elegans expressing human alpha-synuclein. We employed RNAi-mediated silencing, followed by behavioural, functional, and metabolic profiling in relation to suppression of NHR-210 and 231. Our findings revealed that depleting nhr-210 changes dopamine-associated behaviour and mitochondrial function in human alpha synuclein-expressing strains NL5901 and UA44, through a putative target, pgp-9, a transmembrane transporter. Considering the alteration in mitochondrial function and the involvement of a transmembrane transporter, we performed metabolomics study via HR-MAS NMR spectroscopy. Remarkably, substantial modifications in ATP, betaine, lactate, and glycine levels were seen upon the absence of nhr-210. We also detected considerable changes in metabolic pathways such as phenylalanine, tyrosine, and tryptophan biosynthesis metabolism; glycine, serine, and threonine metabolism; as well as glyoxalate and dicarboxylate metabolism. In conclusion, the deficiency of the nuclear hormone receptor nhr-210 in alpha-synuclein expressing strain of C. elegans, results in altered mitochondrial function, coupled with alterations in vital metabolite levels. These findings underline the functional and physiological importance of nhr-210 enrichment in CEPsh glia. Graphical abstract

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Functional implications of NHR-210 enrichment in C. elegans cephalic sheath glia: insights into metabolic and mitochondrial disruptions in Parkinson's disease models

Hameed,

Naseer,

Saxena

et al. 2024

Cell. Mol. Life Sci.

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“…We performed at least two independent experiments for microscopy-mediated quantification assays to treat and study the 100 nematodes for individual groups, as reported in our published literature [ 20 ]. However, the F int.…”

Section: Methodsmentioning

confidence: 99%

Food-Grade Quercetin-Loaded Nanoemulsion Ameliorates Effects Associated with Parkinson’s Disease and Cancer: Studies Employing a Transgenic C. elegans Model and Human Cancer Cell Lines

et al. 2022

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A nanosized food-grade quercetin-loaded nanoemulsion (QNE) system comprising capmul MCM NF (oil) and cremophor RH 40 (surfactant) was developed using a high-speed homogenization technique. The developed QNE was studied for its significant neuroprotective (anti-Parkinsonism) and cytotoxicity (anticancer) effects against Caenorhabditis elegans (C. elegans) strains and human cancer cells, respectively. HR-TEM studies revealed that the QNE was spherical with a mean globule size of ~50 nm. Selected area electron diffraction (SAED) studies results demonstrated that QNE was amorphous. In vivo results show that QNE potentially reduced the α-Syn aggregation, increased mitochondrial and fat content, and improved the lifespan in transgenic C. elegans strain NL5901. QNE significantly downregulated the reactive oxygen species (ROS) levels in wild-type C. elegans strain N2. In vitro results of the MTT assay show that QNE significantly exhibited chemotherapeutic effects in all treated human cancer cells in an order of cytotoxicity: HeLa cells > A549 cells > MIA PaCa-2 cells, based on the IC50 values at 24 h. Conclusively, the QNE showed improved solubility, targetability, and neuroprotective effects against the PD-induced C. elegans model, and also cytotoxicity against human cancer cells and could be potentially used as an anti-Parkinson’s or anticancer agent.

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“…Moreover, it can be generated endogenously during lipid peroxidation reactions and the decomposition of polyunsaturated fatty acids, as well as the metabolism of polyamines and amino acids in the body [ 3 ]. However, it had been reported that ACR was associated with diverse pathological conditions, comprising lung cancer, cardiovascular disease, and neurological diseases [ 4 , 5 , 6 , 7 ]. Studies have found that ACR catabolized endogenous antioxidants and depleted the storage of reduced glutathione in cells, in addition to increasing lipid peroxidation reactions by sparking the reactive oxygen species (ROS) formation [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Acrolein Promotes Aging and Oxidative Stress via the Stress Response Factor DAF-16/FOXO in Caenorhabditis elegans

Song

Xie

et al. 2022

Foods

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For this investigation, Caenorhabditis elegans (C. elegans) served, for the first time, as a model organism to evaluate the toxic effect and possible underlying mechanisms under acrolein (ACR) exposure. The results showed that ACR exposure (12.5–100 μM) shortened the lifespan of C. elegans. The reproductive capacity, body length, body width, and locomotive behavior (head thrash) of C. elegans were diminished by ACR, especially the doses of 50 and 100 μM. Furthermore, ACR significantly enhanced the endogenous ROS levels of C. elegans, inhibited the antioxidant-related enzyme activities, and affected the expression of antioxidant related genes. The increasing oxidative stress level promoted the migration of DAF-16 into the nucleus that was related to the DAF-16/FOXO pathway. It was also confirmed by the significant decrease of the lifespan-shortening trend in the daf-16 knockout mutant. In conclusion, ACR exposure induced aging and oxidative stress in C.elegans, resulting in aging-related decline and defense-related DAF-16/FOXO pathways’ activation.

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Genetic modulators associated with regulatory surveillance of mitochondrial quality control, play a key role in regulating stress pathways and longevity in C. elegans

Cited by 10 publications

References 77 publications

Functional implications of NHR-210 enrichment in C. elegans cephalic sheath glia: insights into metabolic and mitochondrial disruptions in Parkinson's disease models

Functional implications of NHR-210 enrichment in C. elegans cephalic sheath glia: insights into metabolic and mitochondrial disruptions in Parkinson's disease models

Food-Grade Quercetin-Loaded Nanoemulsion Ameliorates Effects Associated with Parkinson’s Disease and Cancer: Studies Employing a Transgenic C. elegans Model and Human Cancer Cell Lines

Acrolein Promotes Aging and Oxidative Stress via the Stress Response Factor DAF-16/FOXO in Caenorhabditis elegans

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