Analysis of expression and posttranslational modification of proteins during hypoxia

Abstract

The cellular responses to hypoxia are complex and characterized by alterations in the expression of a number of genes, including stress-related genes and corresponding proteins that are necessary to maintain homeostasis. The purpose of this article is to review previous and recent studies that have examined the changes in the expression and posttranslational modification of proteins in response to chronic sustained and intermittent forms of hypoxia. A large number of studies focused on the analysis of either the single protein or a subset of related proteins using one-dimensional gel electrophoresis to separate a complex set of proteins from solubilized tissues or cell extracts, followed by immunostaining of proteins using antibodies that are specific to either native or posttranslationally modified forms. On the other hand, only a limited number of studies have examined the global perturbations on protein expression by hypoxia using proteomics approach involving two-dimensional electrophoresis coupled with mass spectrometry. Results derived from specific protein analysis of a variety of tissues and cells showed that hypoxia, depending on the duration and severity of the stimulus, affects the level and the state of posttranslational modification of a subset of proteins that are associated with energy metabolism, stress response, cell injury, development, and apoptosis. Some of these earlier findings are further corroborated by recent studies that utilize a global proteomics approach, and, more importantly, results from these proteomics investigations on the effects of hypoxia provide new protein targets for further functional analysis. The anticipated new information stems from the analysis of expression, and posttranslational modification of these novel protein targets, along with gene expression profiles, offers exciting new opportunities to further define the mechanisms of cellular responses to hypoxia and to control more effectively the clinical consequences of prolonged or periodic lack of oxygen.

Proteomics‐driven progress in neurodegeneration research

“…Overexpression for Bcl-2-like protein 11 was observed in the AD and DS brain [47,95]. Increased levels for Bcl-2 were observed in an animal model of hypoxia [67].…”

“…In an ischemia model, increased expression for the signaling molecules platelet activation factor receptor and retinal guanyl cyclase 2 were observed [68]. Changes in the phosphorylation pattern of adenyl cyclase associated protein 2 and DRP2 were found in an animal model of stroke [128] and of signaling proteins in a hypoxia model [67,127].…”

“…Headaches, fatigue, shortness of breath, nausea, unsteadiness, and sometimes even seizures and coma are some of the reported symptoms. Cellular responses to hypoxia are complex and characterized by alteration in the expression of a series of genes, among which are stress-related genes and their products which are necessary for homeostasis maintenance [67]. Ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue.…”

“…In contrast to hypoxia, ischemia is an absolute or relative shortage of the blood supply to an organ. Animal models of these disorders have been studied by proteomics approaches [67,68].…”

“…In the brain of patients with schizophrenia, decreased levels were observed for leucine aminopeptidase and the translation regulatory protein elongation factor Tu [66]. In a model of hypoxia, increased phosphorylation for the cAMPresponsive element binding protein 1 was observed [67].…”