SUMOylation in peripheral tissues under low perfusion‐related pathological states

Abstract

SUMOylation is described as a posttranslational protein modification (PTM) that is involved in the pathophysiological processes underlying several conditions related to ischemia‐ and reperfusion‐induced damage. Increasing evidence suggests that, under low oxygen levels, SUMOylation might be part of an endogenous mechanism, which is triggered by injury to protect cells within the central nervous system. However, the role of ischemia‐induced SUMOylation in the periphery is still unclear. This article summarizes the results of recent studies regarding SUMOylation profiles in several diseases characterized by impaired blood flow to the cardiorenal, gastrointestinal, and respiratory systems. Our review shows that although ischemic injury per se does not always increase SUMOylation levels, as seen in strokes, it seems that in most cases the positive modulation of protein SUMOylation after peripheral ischemia might be a protective mechanism. This complex relationship warrants further investigation, as the role of SUMOylation during hypoxic conditions differs from organ to organ and is still not fully elucidated.

SUMOtherapeutics for Ischemic Stroke

“…SUMO conjugation of proteins (SUMOylation) was first implicated in the torpor conditioning of the 13-lined ground squirrel (Ictidomys tridecemlineatus). The analogous nature of this physiological mechanism of hibernation to the pathological mechanism of ischemic stroke and arousal to reperfusion has made it a direction for inquiry in the context of neuroprotection [12][13][14]. Postmortem observation of increased SUMOylation within the penumbra of ischemic stroke in human victims has made the potential exploitation of this pathway of clinical interest [15].…”

“…Glioblastomas have been found to overexpress SUMO [22]; increased SUMOylation has been associated with Alzheimer's Disease and Huntington's Disease; and both increased SUMO1ylation and decreased SUMO2/3ylation have been implicated with alpha-synuclein aggregation in Parkinson's disease [27]. Moreover, SUMOylation is known to play a role in cardiac [28,29], renal [30], pulmonary, hepatic and mesenteric ischemic disease processes [14]. These observations, coupled with reports on the critical role of SUMO in cell survival during hyperacute ischemic pathologies such as myocardial infarction [31] make it of particular interest for the management of acute ischemic stroke.…”

SUMOtherapeutics for Ischemic Stroke

“…The SUMO conjugation of proteins (SUMOylation) was first implicated in the torpor conditioning of the 13-lined ground squirrel ( Ictidomys tridecemlineatus ) [ 12 ]. The analogous nature of this physiological mechanism of hibernation to the pathological mechanism of ischemic stroke and arousal to reperfusion has made it a direction for inquiry in the context of neuroprotection [ 12 , 13 , 14 ]. The postmortem observations of increased SUMOylation within the penumbra of ischemic stroke in human victims has made the potential exploitation of this pathway of clinical interest [ 15 ].…”

“…Glioblastomas have been found to overexpress SUMO [ 22 ]; increased SUMOylation has been associated with Alzheimer’s Disease and Huntington’s Disease; and both increased SUMO1ylation and decreased SUMO2/3ylation have been implicated with α-synuclein aggregation in Parkinson’s disease [ 29 ]. Moreover, SUMOylation is known to play a role in cardiac [ 30 , 31 ], renal [ 32 ], pulmonary, hepatic, and mesenteric ischemic disease processes [ 14 ]. These observations, coupled with reports on the critical role of SUMO in cell survival during hyperacute ischemic pathologies, such as myocardial infarction [ 33 ], make it of particular interest for the management of acute ischemic stroke.…”

“…The neuroprotective effects of SUMOylation have been widely observed both in vitro and in vivo [ 14 ]. Due to the role of SUMO as the “modifier of modifiers” and the great physiological distance between the act of SUMOylation and its ultimate effect; a comprehensive pattern of association between end-effects and neuroprotection remains to be clearly demonstrated [ 14 ].…”