Induction of Chemerin on Autophagy and Apoptosis in Dairy Cow Mammary Epithelial Cells

Abstract

Simple SummaryThe process of mammary gland involution during the early is accomplished by both apoptosis and autophagy. Chemerin, a novel adipocytokine, plays a pivotal role in immune response and lipid metabolism, which was involved in the regulation of programmed cell death. This study focused on the relationship between autophagy and apoptosis in the presence of Chemerin in bovine mammary epithelial cells (BMECs). The results indicated that Chemerin could activate the complete autophagy process and induce apoptotic cascade in BMECs. The addition of Chloroquine (CQ), an inhibitor of autophagy, prompted Chemerin to have more obvious effects on apoptosis-related factors, which suggests that Chemerin-induced autophagy involves the intrinsic apoptotic pathway of BMECs. We found that the pro-apoptotic potential of Chemerin is further enhanced under conditions in which autophagy is effectively inhibited. Thus, exploring the role of autophagy and apoptosis on the involution of mammary epithelial cells will undoubtedly be of great importance in productivity improvement of dairy animals. AbstractInvolution of the mammary gland is a complex process controlled by various endocrine hormones and cytokine. As a novel adipocytokine, Chemerin not only plays a pivotal role in physiological and pathological processes such as immune response and lipid metabolism, but is also involved in the regulation of programmed cell death, including autophagy and apoptosis. The purpose of the present study was to elucidate whether autophagy and apoptosis of bovine mammary epithelial cells (BMECs) was triggered by Chemerin. BMECs were cultured and treated with Chemerin in vitro. The expression of autophagosome-forming marker, microtubule-associated protein 1 light chain 3 II (LC3-II) and sequestosome-1 (SQSTM 1, best known as p62), a substrate of autophagosome degradation were detected. The result showed that Chemerin significantly decreased the expression of p62 and markedly induced the conversion of LC3-I to LC3-II. The ratio of Bcl2-associated X and B-cell lymphoma-2 (Bax/Bcl-2) and the activity of caspase-3 were up-regulated after being treated by Chemerin, and the apoptotic rate was also significantly increased. These results suggested that Chemerin promoted the occurrence of autophagy and apoptosis in BMECs. Chloroquine (CQ), which is an inhibitor of autophagy. To explore effects of Chemerin on apoptosis, we prevented Chemerin-induced autophagy by pre-adding CQ in BMECs. Interestingly, this part of the experiment helped us find that all effects of Chemerin on apoptosis of BMECs could be enhanced with the inhibition of autophagy. Our study demonstrates that Chemerin-induced autophagy and apoptosis are mutually regulated in BMECs, but the specific mechanism remains to be further researched.

Chemerin/ChemR23 regulates cementoblast function and tooth resorption in mice via inflammatory factors

“…Our study confirms that chemerin induces cementoblast apoptosis, as demonstrated by the increased level of cleaved caspase 3 and the increased number of apoptotic cells detected by flow cytometry in chemerin‐treated cells compared with control cells. This conclusion is consistent with the findings of other studies showing that chemerin can induce apoptosis in other kinds of cells 24,25 . The results of the CCK‐8 assay showed fold increases in relative cell number in the chemerin‐treated group compared with the unstimulated control group at 12 hours.…”

“…This conclusion is consistent with the findings of other studies showing that chemerin can induce apoptosis in other kinds of cells. 24,25 The results of the CCK-8 assay showed fold increases in relative cell number in the chemerin-treated group compared with the unstimulated control group at 12 hours. No significant differences were observed at 24 or 48 hours, indicating that chemerin did not exhibit cytotoxicity in OCCM-30 cells at the doses and durations used.…”

Chemerin Regulates Epithelial Barrier Function of Mammary Glands in Dairy Cows

“…During this process, macrophages are recruited to remove apoptotic cells, resulting in the occupation of stromal cells in tissue [ 25 ]. Additionally, Hu et al reported that chemerin induced the activities of autophagy and apoptosis in cultured bovine mammary epithelial cells (BMECs) [ 26 ]. The chemerin-induced apoptosis was further activated when autophagy was inhibited by chloroquine.…”

“…The chemerin-induced apoptosis was further activated when autophagy was inhibited by chloroquine. This implicates that chemerin can induce the programmed death of bovine mammary epithelial cells during the process of involution and maintenance of the mammary gland during the dry-off period [ 26 ]. Therefore, chemerin was suggested to act as a chemokine to antigen-presenting cells (APCs), and also as an inducer of apoptosis in involuting/involuted mammary glands, which supports the closed relationship between chemerin and the immune response in mammary glands.…”

Adipose-Derived Molecules–Untouched Horizons in Alzheimer’s Disease Biology

“…Furthermore, Aβ42 stimulates CMKLR1-RBL cells and primary glial cells to internalize the Aβ42-CMKLR1 complex, which helps in the clearance of Aβ42 (Kulig et al, 2011). Very recently, chemerin was reported to induce autophagy in bovine mammary epithelial cells (Hu et al, 2019). Therefore, it is reasonable to speculate that it might induce autophagy in microglial cells also, which needs to be explored.…”