Circulating membrane-derived microvesicles in redox biology

Abstract

Microparticles or microvesicles (MV) are sub-cellular membrane blebs shed from all cells in response to various stimuli. MVs carry a battery of signaling molecules, many of them related to redox-regulated processes. The role of MVs, either as a cause or result of cellular redox signaling has been increasingly recognized over the past decade. This is in part due to advances in flow cytometry and its detection of MVs. Notably, recent studies have shown circulating MVs from platelets and endothelial cells drive reactive species-dependent angiogenesis; circulating MVs in cancer alter the microenvironment and enhance invasion through horizontal transfer of mutated proteins and nucleic acids, and harbor redox-regulated matrix metalloproteinases and pro-coagulative surface molecules; and circulating MVs from RBCs and other cells modulate cell-cell interactions through scavenging or production of nitric oxide and other free radicals. While our recognition of MVs in redox-related processes is growing, especially in the vascular biology field, much remains unknown regarding the various biologic and pathologic functions of MVs. Like reactive oxygen and nitrogen species, MVs were originally believed to have a solely a pathological role in biology. And like our understanding of reactive species, it is now clear that MVs also play an important role in normal growth, development, and homeostasis. We are just beginning to understand how MVs are involved in various biological processes—developmental, homeostatic and pathological—and the role of MVs in redox signaling is an rich and exciting area of investigation.

Extracellular Vesicles Mediate Radiation-Induced Systemic Bystander Signals in the Bone Marrow and Spleen

“…However, Dutta et al showed that EVs isolated from the cell culture supernatant of human breast cancer cell lines were able to induce phosphorylation of key proteins (ataxia-teleangiectasia mutated (ATM), H2AX, Chk1, and p53) involved in DNA damage response in primary mammary epithelial cells in vitro by transmitting signals that led to ROS production and a consequential oxidative stress in the EV-recipient cells (54, 55). The role of EVs in inducing oxidative stress and mediating redox-regulated signaling processes in EV-recipient cells has been shown by several other recent reports as well (55, 56). Fontaine et al proved the implicit role of EVs in this process, since the increased oxidative stress in the vascular wall of patients after coronary surgery disappeared if using EV-depleted plasma (56).…”

Short-term particulate matter exposure induces extracellular vesicle release in overweight subjects

“…It is worth noting that the role of MVs in redox signaling has been regarded as a very promising area of investigation, as recently reviewed by Larson and collaborators (Larson et al, 2014). According to our data, the most pronounced PM effect was observed in endothelial MVs.…”

“…Based on their size, they can be classified as exosomes (30–130 nm) and microvesicles (MVs, 130–700 nm). Exosomes are thought to be constitutively generated, stored, and released from the endosomal system, whereas MVs are shed from the plasma membrane in response to specific stimuli (Larson et al, 2014). MVs, in particular, are released from the external membrane of many, if not all, cell types.…”

Oxidative and other posttranslational modifications in extracellular vesicle biology

“…Oxidative stress can also enhance EV release [30]. Tertbutyl-hydroperoxide-treated rat hepatocytes showed increased vesiculation, which depended on calcium, and the calciumdependent protease, calpain [31].…”

“…Some of the redox-active proteins carried by EVs are specifically associated with blood plasma-derived EVs [30], and this may bear relevance to immune regulation. Cell surface molecules, underlying redox regulation, such as certain adhesion molecules (e.g.…”