ArticleThe Journal of biological chemistry2008
Leukocyte antigen-related protein tyrosine phosphatase negatively regulates hydrogen peroxide-induced vascular smooth muscle cell apoptosis.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
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- L-lysine protects C2C12 myotubes and 3T3-L1 adipocytes against high glucose damages and stresses.PloS one · 2019Article
- Aquaporin 1, Nox1, and Ask1 mediate oxidant-induced smooth muscle cell hypertrophy.Cardiovascular research · 2013Article
- New role of JAK2/STAT3 signaling in endothelial cell oxidative stress injury and protective effect of melatonin.PloS one · 2013Article
- Angiopoietin-1-expressing adipose stem cells genetically modified with baculovirus nanocomplex: investigation in rat heart with acute infarction.International journal of nanomedicine · 2012Article
- Role for miR-204 in human pulmonary arterial hypertension.The Journal of experimental medicine · 2011Article
- Disruption of astrocyte STAT3 signaling decreases mitochondrial function and increases oxidative stress in vitro.PloS one · 2010Article
- Activator of G protein signaling 8 (AGS8) is required for hypoxia-induced apoptosis of cardiomyocytes: role of G betagamma and connexin 43 (CX43).The Journal of biological chemistry · 2009Article
- Mechanical properties of the extracellular matrix alter expression of smooth muscle protein LPP and its partner palladin; relationship to early atherosclerosis and vascular injury.Journal of muscle research and cell motility · 2009Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Reactive oxygen species (ROS) have been implicated in vascular smooth muscle cell (VSMC) apoptosis, a hallmark of advanced atherosclerotic lesions. Transient oxidation and inactivation of protein-tyrosine phosphatases play a critical role in cellular response to ROS production. However, the function of leukocyte antigen-related (LAR) protein-tyrosine phosphatase in ROS signaling is not known. To determine the expression of LAR in ROS-induced apoptosis, we investigated hydrogen peroxide-induced cell death and signaling in aortic VSMCs from wild-type and LAR(-/-) mice. Histone-associated DNA fragmentation and caspase-3/7 activity were significantly enhanced, mitochondrial membrane integrity was compromised, and cell viability was significantly decreased following H(2)O(2) treatment in LAR(-/-) VSMCs compared with wild-type cells. Stronger and sustained increase in autophosphorylation and activity of Fyn, an Src family tyrosine kinase, was observed in LAR(-/-) cells compared with wild-type cells following H(2)O(2) treatment. LAR binds to activated Fyn in H(2)O(2)-treated VSMCs, and recombinant LAR dephosphorylates phosphorylated-Fyn in vitro. In addition, LAR deficiency enhanced H(2)O(2)-induced phosphorylation of Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), and p38 mitogen-activated protein kinase (MAPK). PP2, a Fyn-specific inhibitor, blocked JAK2, STAT3, and p38 MAPK activation and significantly attenuated apoptosis induced by H(2)O(2). AG490, a JAK2-specific inhibitor, significantly attenuated H(2)O(2)-induced apoptosis, and blocked H(2)O(2)-induced activation of STAT3, but not p38 MAPK in both wild-type and LAR(-/-) VSMCs. Attenuation of Fyn expression by short hairpin RNA significantly decreased H(2)O(2)-induced downstream signaling and apoptosis in VSMCs. Together, these data indicate that LAR regulates Fyn/JAK2/STAT3 and Fyn/p38 MAPK pathways involved in ROS-induced apoptosis.
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