Biology subjects

Liang, A.

Publications and source records attributed to Liang, A..

20 records · Page 2Linked to original sources

bioRxiv2018

Dimethylarsenic acid (DMA) accumulation positively correlates with realgar-induced subchronic toxicity in rats

The toxicity of realgar depends largely on different arsenic species accumulation and distribution in the body. Here, after continuous oral administration of different doses of realgar for 90 days and subsequent 60-day withdrawal period, clinical observations, food consumption, body weights, blood biochemistry, hematology, and histomorphological examination of rats were performed. Realgar 40mg{middle dot}kg-1{middle dot}d-1 and 170 mg{middle dot}kg-1{middle dot}d-1 of realgar (which is equivalent to 40-fold and 100-fold the maximum clinical dose, respectively) can cause toxicity in rats, including degreased body weight, peripheral blood neutrality abnormal ratio of granulocytes and lymphocytes, hypercoagulability of the blood, liver and kidney tissue damage, liver and kidney may be the main toxic target organs of realgar. The no observed adverse effect level (NOAEL) dose is 10 mg{middle dot}kg-1. At the same time, the content and distribution of arsenic species in tissues were determined. The content of total arsenic (tAs) and Dimethylarsenic acid (DMA) in the tissues of the realgar group was significantly higher than those of the control group. After 60 days of discontinuation, the DMA content in the realgar group decreased, but it was still higher than that in the control group, and liver and kidney damage occurred during the administration period basically returned to normal. Therefore, the authors speculated that when the DMA content in the tissue exceeds a certain range, liver and kidney toxicity will be induced. However, when the DMA content is lower than the above threshold after drug withdrawal, the liver and kidney lesions can return to normal.

pharmacology and toxicology↗

bioRxiv2018

Atlastins mediate selective autophagy of the endoplasmic reticulum

The selective lysosomal degradation (autophagy) of entire organelles is required for cellular homeostasis, and its dysregulation is involved in degenerative disorders such as Parkinsons Disease. While autophagy of mitochondria (mitophagy) is becoming better understood, other forms of organelle autophagy are relatively unexplored. Here we develope multiple quantitative assays to measure organelle autophagy using flow cytometry, microscopy, and Western blotting. Focusing on autophagy of the endoplasmic reticulum (ER-phagy), we show that these assays allow facile measurement of ER-phagy, and that ER-phagy is inhibited by knockdown of either core autophagy components or the recently reported FAM134B ER-phagy receptor. Using these assays, we further identify that Atlastins, the ER-resident GTPases involved in ER membrane morphology, are key positive effectors of ER-phagy. Atlastin-depleted cells have decreased ER-phagy under starvation conditions, and Atlastins role in ER-phagy requires both a functional GTPase domain and proper ER localization. The three Atlastin family members functionally compensate for one another during ER-phagy and may form heteromeric complexes with one another. We also find that Atlastins act downstream of the FAM134B ER-phagy receptor. We propose that during ER-phagy, Atlastins remodel ER membrane to separate pieces of FAM134B-marked ER for efficient autophagosomal engulfment. Human mutations in Atlastins led to hereditary spastic paraplegia, and our results suggest that this disease may be linked to deficiencies in ER-phagy rather than ER morphology.

cell biology↗