Bcl‐2‐associated athanogene 5 overexpression attenuates catecholamine‐induced vascular endothelial cell apoptosis

Abstract

Bcl-2 associated athanogene 5 (Bag5) is a novel endoplasmic reticulum (ER) regulator. However, its role in catecholamine-induced endothelial cells damage has not been fully understood. In our study, catecholamine was used to mimic hypertensionrelated endothelial cell damage. Then, western blots, enzyme-linked immunosorbent assay, immunofluorescence, quantitative polymerase chain reaction and pathway analysis were conducted to analyze the role of Bag5 in endothelial cell damage in response to catecholamine. Our results indicated that the endothelial cell viability was impaired by catecholamine. Interestingly, Bag5 overexpression significantly reversed endothelial cell viability. Mechanistically, Bag5 overexpression inhibited ER stress, attenuated oxidative stress and repressed inflammation in catecholaminetreated endothelial cells. These beneficial effects finally contributed to endothelial cell survival under catecholamine treatment. Pathway analysis demonstrated that Bag5 was under the control of the mitogen-activated protein kinase (MAPK)-extracellular-signal-regulated kinase (ERK) signaling pathway. Reactivation of the MAPK-ERK pathway could upregulate Bag5 expression and thus promote endothelial cell survival through inhibiting oxidative stress, ER stress, and inflammation. Altogether, our results illustrate that Bag5 overexpression sustains endothelial cell survival in response to catecholamine treatment. This finding identifies Bag5 downregulation and the inactivated MAPK-ERK pathway as potential mechanisms underlying catecholamine-induced endothelial cell damage.

Melatonin Attenuates ox-LDL-Induced Endothelial Dysfunction by Reducing ER Stress and Inhibiting JNK/Mff Signaling

“…ER-related cell apoptosis is characterized by increased levels of CHOP and caspase-12 [14,15]. In addition, previous studies have reported a close relationship between endothelial dysfunction and ER stress [16]. Excessive ER stress promotes calcium overload, leading to spasms in endothelial cells [17].…”

BAG5 regulates HSPA8-mediated protein folding required for sperm head-tail coupling apparatus assembly

“…Given that BAG5 is a co-chaperon protein and its biological locations are cytoplasm and endoplasmic reticulum (Bruchmann et al, 2013 ; Hakui et al, 2022 ; Zhu et al, 2021 ), we then examined if BAG5 is co-localized with the markers (ERP72) of the endoplasmic reticulum using IF assays. To this end, we first transfected BAG5-3X Flag into the HEK293F cell line in vitro and found that BAG5 could co-localize with ERP72 (Fig.…”

Role of BAG5 in Protein Quality Control: Double-Edged Sword?

“…Similarly, another recent study reported that BAG5 acts as an ER stress regulator and its expression contributes to maintaining endothelial cell viability and protects cells from endothelial dysfunction ( Zhu et al, 2021 ). This study found that catecholamine-dependent endothelial dysfunction immensely causes an increase in oxidative stress via augmenting ROS production and decreasing the levels of antioxidant factors viz.…”

“…Intriguingly, MAPK-ERK activation using a pharmacological agonist reversed the decline in BAG expression in the dysfunctional cells. This indicated that catecholamine-dependent BAG5 downregulation was possible because of MAPK-ERK inactivation and reactivation of MAPK-ERK abrogated the endoplasmic reticulum stress, oxidative stress, and improved the cell survival via modulating MAPK/ERK signaling and BAG5 transcription ( Zhu et al, 2021 ). The role of BAG5 as a stress regulator is further substantiated by a very recent study which revealed that exposure of primary neuronal cultures to H 2 O 2 for 6 h induced oxidative stress.…”