Copper Induces Apoptosis Through Endoplasmic Reticulum Stress in Skeletal Muscle of Broilers

Abstract

The purpose of this research was to investigate whether copper (Cu) exposure could induce apoptosis via endoplasmic reticulum stress (ERS) in skeletal muscle of broilers. A total of 240 one-day-old chickens were randomly divided into four groups by free access; the diets are as follows: control diet (Cu 11 mg/kg, control group) and high level of Cu diets (Cu 110 mg/kg, group I; Cu 220 mg/kg, group II; Cu 330 mg/kg, group III). The skeletal muscle tissues were collected on day 49 for further examination. The content of Cu, histopathology, and the expression levels of the genes and proteins related to ERS and apoptosis were detected. Results showed that the Cu levels in skeletal muscle were increased in a dose-dependent manner. Meanwhile, the spaces between the muscle fibers were wider with the increase of Cu content, and the myolysis was observed in group III. Besides, the mRNA expression levels of GRP78, GRP94, eIF2α, ATF6, XBP1, CHOP, Caspase-12, and Caspase3 were markedly increased in treated groups compared with control group, and the protein expression levels of GRP78, Caspase3, Active-Caspase3 and JNK were significantly elevated with the increase of dietary Cu. In summary, these findings suggested that Cu could induce apoptosis through ERS in skeletal muscle of broilers.

Exposure to copper activates mitophagy and endoplasmic reticulum stress‐mediated apoptosis in chicken (Gallus gallus) cerebrum

“…To a certain extent, UPR is a unique mechanism to restore and maintain ER harmony, while long‐term and chronic ER stress can induce apoptosis to eliminate damaged cells. A recent research indicated that manganese can induce apoptosis via ER stress pathway to cause neurotoxicity in rat striatum, 15 and similar results were found in skeletal muscle of broilers with Cu exposure 16 …”

“…Wu et al 43 has found that CuSO 4 can induce hepatic apoptosis via ER stress pathway in activating CHOP, JNK, and Caspase12 signaling pathway. In skeletal muscle of broilers, Cu triggers apoptosis through ER stress 16 . Homoplastically, phenomenon also can be observed in duck renal tubular epithelial cells 44 .…”

“…In skeletal muscle of broilers, Cu triggers apoptosis through ER stress. 16 Homoplastically, phenomenon also can be observed in duck renal tubular epithelial cells. 44 As for Caspase12, a vital and unique protein located in the ER membrane, can be specifically triggered by ER stress when ER calcium homeostasis disruption and too much protein accumulation in ER.…”

“…A recent research indicated that manganese can induce apoptosis via ER stress pathway to cause neurotoxicity in rat striatum, 15 and similar results were found in skeletal muscle of broilers with Cu exposure. 16 Imbalances of cerebrum Cu homeostasis have been confirmed to increase several neurogenic diseases, such as Wilson's disease and Alzheimer's disease. 17 1.…”

Sleep fragmentation exacerbates myocardial ischemia‒reperfusion injury by promoting copper overload in cardiomyocytes

“…Moreover, evidence has proven the detrimental effect of copper overload. Cellular copper overload activates the apoptosis pathway via endogenous and exogenous pathways 17 – 19 . On the other hand, copper overload also leads to cuproptosis, a recently newly identified, copper-dependent type of cell death characterized by loss of iron-sulfur cluster protein, reduced levels of lipoylated proteins and increased oligomerization of DLAT 20 .…”