Extracellular vesicles released from cells exposed to reactive oxygen species increase annexin A2 expression and survival of target cells exposed to the same conditions

Abstract

Annexin A2 (AnxA2) is present in multiple cellular compartments and interacts with numerous ligands including calcium, proteins, cholesterol, negatively charged phospholipids and RNA. These interactions are tightly regulated by its post-translational modifications. The levels of AnxA2 and its Tyr23 phosphorylated form (pTyr23AnxA2) are increased in many cancers and the protein is involved in malignant cell transformation, metastasis and angiogenesis. Our previous studies of rat pheochromocytoma (PC12) cells showed that reactive oxygen species (ROS) induce rapid, simultaneous and transient dephosphorylation of nuclear AnxA2, most likely associating with PML bodies, while AnxA2 associated with F-actin at the cell cortex undergoes Tyr23 phosphorylation. The pTyr23AnxA2 in the periphery of the cells is incorporated into intraluminal vesicles of multivesicular endosomes and subsequently released to the extracellular space. We show here that extracellular vesicles (EVs) from cells exposed to ROS prime untreated PC12 cells to better tolerate subsequent oxidative stress, thus enhancing their survival. There is an increase in the levels of pTyr23AnxA2 and AnxA2 in the primed cells, suggesting that AnxA2 is involved in their survival. This increase is due to an upregulation of AnxA2 expression both at the transcriptional and translational levels after relatively short term (2 h) exposure to primed EVs.

Annexin A2 regulates Mycoplasma bovis adhesion and invasion to embryo bovine lung cells affecting molecular expression essential to inflammatory response

“…First, we demonstrated that ANXA2 mRNA and protein levels increased during the invasion of M. bovis , and S100A10, the interacting protein of ANXA2, was also upregulated in M. bovis infection, indicating ANXA2 might together with S100A10 participate in its infection. Increased ANXA2 expression has been observed in a variety of cancers ( 35 ), viral infections ( 18 ), and bacterial invasion processes such as Escherichia coli ( 36 ) and Cryptococcus neoformans ( 27 ). Previous research has discovered that ANXA2 contributes to M. hyorhinis infection by interacting with p37 at their N-terminal domain ( 23 ).…”

“…Validation of expression patterns of selected genes using qPCR. ANXA2 expression has been observed in a variety of cancers (35), viral infections (18), and bacterial invasion processes such as Escherichia coli (36) and Cryptococcus neoformans (27).…”

Microvesicles: ROS scavengers and ROS producers

“…MVs derived from ischemic muscles (56), plasma of patients with lupus [99] or neutrophils infected with Mycobacterium tuberculosis [70] were shown to induce ROS in mononuclear cells, neutrophils and macrophages, respectively. However, MVs derived from cells exposed to ROS induced ROS tolerance in PC12 cells [100]. MVs derived from tumour cells showed a similar behavior; they can contain antioxidant enzymes [72] or can modulate the activity of human monocytes by increasing ROS, among other effects [73].…”