+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Complete transglutaminase 2 ablation results in reduced stroke volumes and astrocytes that exhibit increased survival in response to ischemia



Complete transglutaminase 2 ablation results in reduced stroke volumes and astrocytes that exhibit increased survival in response to ischemia



Neurobiology of Disease 45(3): 1042-1050



Transglutaminase 2 (TG2) is a very multifunctional protein that is ubiquitously expressed in the body. It is a Ca(2+)-dependent transamidating enzyme, a GTPase, as well as a scaffolding protein. TG2 is the predominant form of transglutaminase expressed in the mammalian nervous system. Previously, it was shown that TG2 can affect both cell death and cell survival mechanisms depending on the cell type and the stressor. In the case of ischemic stress, TG2 was previously shown to play a protective role in the models used. For example in hTG2 transgenic mice, where TG2 is overexpressed only in neurons, middle cerebral artery ligation (MCAL) resulted in smaller infarct volumes compared to wild type mice. In this study TG2 knock out mice were used to determine how endogenous TG2 affected stroke volumes. Intriguingly, infarct volumes in TG2 knock out mice were significantly smaller compared to wild type mice. As expected, primary neurons isolated from TG2 knock out mice showed decreased viability in response to oxygen-glucose deprivation. However, primary astrocytes that were isolated from TG2 knock out mice were resistant to oxygen-glucose deprivation in situ. Both wild type and knock out neurons were protected against oxygen glucose deprivation when they were co-cultured with astrocytes from TG2 knockout mice. Therefore, the decreased stroke volumes observed in TG2 knock out mice after MCAL, can be correlated with the protective effects of TG2 knock out in astrocytes in response to oxygen glucose deprivation in situ. These findings suggest that neuron-astrocyte crosstalk plays a significant role in mediating ischemic cell death and that TG2 differentially impacts cell survival depending on cell context.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 052260669

Download citation: RISBibTeXText

PMID: 22198379

DOI: 10.1016/j.nbd.2011.12.023


Related references

GFAP-deficient astrocytes are capable of stellation in vitro when cocultured with neurons and exhibit a reduced amount of intermediate filaments and an increased cell saturation density. Experimental Cell Research 239(2): 332-343, 1998

Hypercontractile female hearts exhibit increased S-nitrosylation of the L-type Ca2+ channel alpha1 subunit and reduced ischemia/reperfusion injury. Circulation Research 98(3): 403-411, 2006

Free fatty acid fractions from some vegetable oils exhibit reduced survival time-shortening activity in stroke-prone spontaneously hypertensive rats. Lipids 33(7): 655-661, 1998

Increased expression of the neurofibromatosis 1 (NF1) gene product, neurofibromin, in astrocytes in response to cerebral ischemia. Journal of Neuroscience Research 43(2): 246-253, 1996

U18666A Treatment Results in Cholesterol Accumulation, Reduced Na(+), K(+)-ATPase Activity, and Increased Oxidative Stress in Rat Cortical Astrocytes. Lipids 50(10): 937-944, 2015

Differences between global left ventricular stroke volume and the sum of regional stroke volumes in the dog during acute myo cardial ischemia. Journal Of Nuclear Medicine: P81, 1982

VEGFR-2-mediated increased proliferation and survival in response to oxygen and glucose deprivation in PlGF knockout astrocytes. Journal of Neurochemistry 107(3): 756-767, 2008

Increased survival and reduced proteinuria in salt loaded stroke prone spontaneously hypertensive rats shrsp treated with captopril. FASEB Journal 2(5): ABSTRACT 6309, 1988

Survival of patients with hepatocellular carcinoma (HCC) treated by percutaneous radio-frequency ablation (RFA) is affected by complete radiological response. Plos one 8(7): E70016, 2013

Human epileptic astrocytes exhibit increased gap junction coupling. Glia 15(2): 195-202, 1995

Improvement of survival in Polish stroke patients is related to reduced stroke severity and better control of risk factors: the Krakow Stroke Database. Archives of Medical Science 12(3): 552-555, 2016

Transgenic mice overexpressing in the brain urokinase-type plasminogen activator exhibit reduced food consumption, reduced body weight and size and increased longevity. Fibrinolysis 10(Suppl. 3): 85, 1996

Spinal muscular atrophy astrocytes exhibit abnormal calcium regulation and reduced growth factor production. Glia 61(9): 1418-1428, 2013