Deguo Du

Florida Atlantic University; Boca Raton FL, United States of America

Dan Du

Sichuan University; Chengdu, China

Du D et al. (2011) Biochemistry "A kinetic aggregation assay allowing selective and sensitive amyloid- quantification in cells and tissues."

Murray AN, Cohen E, Kim HE, Du D, Simkovsky R, Kelly JW, Dillin A

[Biochemistry, 2011]

The process of amyloid- (A) fibril formation is genetically and pathologically linked to Alzheimer's disease (AD). Thus, a selective and sensitive method for quantifying A fibrils in complex biological samples allows a variety of hypotheses to be tested. Herein, we report the basis for a quantitative in vitro kinetic aggregation assay that detects seeding-competent A aggregates in mammalian cell culture media, in Caenorhabditis elegans lysate, and in mouse brain homogenate. Sonicated, proteinase K-treated A fibril-containing tissue homogenates or cell culture media were added to an initially monomeric A(1-40) reporter peptide to seed an in vitro nucleated aggregation reaction. The reduction in the half-time (t(50)) of the amyloid growth phase is proportional to the quantity of seeding-competent A aggregates present in the biological sample. An ion-exchange resin amyloid isolation strategy from complex biological samples is demonstrated as an alternative for improving the sensitivity and linearity of the kinetic aggregation assay.

Lu M et al. (2020) ACS Omega "Exploring the Toxicology of Depleted Uranium with Caenorhabditis elegans."

Li Y, Lu Y, Li H, Lu M, Wang X, Wang H

[ACS Omega, 2020]

Depleted uranium (DU) is an emerging heavy metal pollutant with considerable environmental and occupational concerns. Its radiotoxicity is known to be low. However, its chemical toxicity should not be ignored. In order to explore the chemical toxicity of DU, the effects of uranyl nitrate, prepared from DU, on the model organism <i>Caenorhabditis elegans</i> were investigated. Chronic exposure to DU did not affect the lifespan or reproduction of the worm. DU had little effect on the physiological processes of <i>C. elegans</i>. Additionally, DU treatment did not make <i>C. elegans</i> more susceptible to UV, heat, or oxidative stress. Interestingly, chronic exposure of DU decreased the <i>in vivo</i> reactive oxygen species-scavenging ability through inhibiting the expression of antioxidant genes <i>ctl</i>-1, <i>ctl</i>-2, <i>ctl</i>-3, <i>gst</i>-7, and <i>gst</i>-10. Chronic but not acute exposure of DU induced a statistically significant degeneration of the dopaminergic (DAergic) neurons of treated worms and promoted the increase of -synuclein aggregation and DAergic neurotoxicity. These findings may raise the public concerns regarding DU as an etiologic agent of Parkinson's disease and underline its potential neurotoxicity.

Picture from Ziel JW et al. (2009) Gene Expr Patterns "An expression screen for RhoGEF genes involved in C. elegans ...."

K07D4.7b is specifically active within the AC at the time of invasion and was not expressed within the VU/DU cells. First 2 panels on the left, anchor cell expression, to the right DU/VU cell expression.

Picture from Ziel JW et al. (2009) Gene Expr Patterns "An expression screen for RhoGEF genes involved in C. elegans ...."

T19E10.1/ ect-2 5'CRE activity was detected in the DU/VU cells, L3 stage.

Jiang GC et al. (2009) Toxicol Sci "Caenorhabditis elegans metallothioneins protect against toxicity induced by depleted uranium."

Evje L, Aschner M, Sturzenbaum SR, Jiang GC, Syversen T, Hughes S

[Toxicol Sci, 2009]

Depleted uranium (DU) is a dense and heavy metal used in armor, ammunition, radiation shielding, and counterbalances. The military usage has led to growing public concern regarding the health effects of DU. In this study, we used the nematode, Caenorhabditis elegans, to evaluate the toxicity of DU and its effects in knockout strains of metallothioneins (MTs), which are small thiol-rich proteins that have numerous functions, such as metal sequestration, transport, and detoxification. We examined nematode viability, the accumulation of uranium, changes in MT gene expression by quantitative reverse transcription-PCR, and the induction of green fluorescent protein under the control of the MT promoters, following exposure to DU. Our results indicate that (1) DU causes toxicity in a dose-dependent manner; (2) MTs are protective against DU exposure; and (3) nematode death by DU is not solely a reflection of intracellular uranium concentration. (4) Furthermore, only one of the isoforms of MTs, metallothionein-1 (mtl-1), appears to be important for uranium accumulation in C. elegans. These findings suggest that these highly homologous proteins may have subtle functional differences and indicate that MTs mediate the response to DU.

Picture from Ziel JW et al. (2009) Gene Expr Patterns "An expression screen for RhoGEF genes involved in C. elegans ...."

ect-2 is active broadly within the central gonad at the mid-to-late L3 stage, being expressed in both the AC (arrows) and the VU/DU cells (brackets). First 2 panels on the left, anchor cell expression, to the right DU/VU cell expression.

Picture from Ziel JW et al. (2009) Gene Expr Patterns "An expression screen for RhoGEF genes involved in C. elegans ...."

f55c7.7a,b is active broadly within the central gonad at the mid-to-late L3 stage, being expressed in both the AC (arrows) and the VU/DU cells (brackets). First 2 panels on the left, anchor cell expression, to the right DU/VU cell expression.

Picture from Ziel JW et al. (2009) Gene Expr Patterns "An expression screen for RhoGEF genes involved in C. elegans ...."

K07D4.7a is active broadly within the central gonad at the mid-to-late L3 stage, being expressed in both the AC (arrows) and the VU/DU cells (brackets). First 2 panels on the left, anchor cell expression, to the right DU/VU cell expression.