p38 mitogen-activated protein kinase activation during platelet storage: consequences for platelet recovery and hemostatic function in vivo.

Blood 2010 Mar 30;115(9):1835-42. Epub 2009 Nov 30.

Immune Disease Institute, Boston, MA, USA.

Platelets undergo several modifications during storage that reduce their posttransfusion survival and functionality. One important feature of these changes, which are known as platelet storage lesion, is the shedding of the surface glycoproteins GPIb-alpha and GPV. We recently demonstrated that tumor necrosis factor-alpha converting enzyme (TACE/ADAM17) mediates mitochondrial injury-induced shedding of adhesion receptors and that TACE activity correlates with reduced posttransfusion survival of these cells. We now confirm that TACE mediates receptor shedding and clearance of platelets stored for 16 hours at 37 degrees C or 22 degrees C. We further demonstrate that both storage and mitochondrial injury lead to the phosphorylation of p38 mitogen-activated kinase (MAPK) in platelets and that TACE-mediated receptor shedding from mouse and human platelets requires p38 MAP kinase signaling. Protein kinase C, extracellular regulated-signal kinase MAPK, and caspases were not involved in TACE activation. Both inhibition of p38 MAPK and inactivation of TACE during platelet storage led to a markedly improved posttransfusion recovery and hemostatic function of platelets in mice. p38 MAPK inhibitors had only minor effects on the aggregation of fresh platelets under static or flow conditions in vitro. In summary, our data suggest that inhibition of p38 MAPK or TACE during storage may significantly improve the quality of stored platelets.

Download full-text PDF

http://dx.doi.org/10.1182/blood-2009-03-211706DOI Listing
March 2010
Get 20% Off Journals at LWW.com

Similar Publications

Combined effect of chrysin and apigenin on inhibiting the development and progression of colorectal cancer by suppressing the activity of P38-MAPK/AKT pathway.

IUBMB Life 2021 Feb 24. Epub 2021 Feb 24.

Department of gastroenterology, Shengli oilfield central hospital, Dongying City, China.

Either apigenin or chrysin alone has been found to exert anti-inflammatory and tumor suppressive effect. However, the combined effect of apigenin and chrysin on colorectal cancer (CRC) has not been fully clarified. We attempted to explore the effect of chrysin and apigenin on CRC and its related mechanism. Read More

View Article and Full-Text PDF
February 2021

Radioprotective Potential of Nutraceuticals and their Underlying Mechanism of Action.

Anticancer Agents Med Chem 2021 Feb 22. Epub 2021 Feb 22.

Faculty of Pharmacy and Biochemistry, Academic Department of Pharmacology, Bromatology and Toxicology, Centro Latinoamericano de Enseñanza e Investigación en Bacteriología Alimentaria (CLEIBA), Universidad Nacional Mayor de San Marcos, Lima15001. Peru.

Radiations are an efficient treatment modality in cancer therapy. Besides the treatment effects of radiations, the ionizing radiations interact with biological systems and generate reactive oxygen species that interfere with the normal cellular process. Previous investigations of synthetic radioprotectors have shown less effectiveness, mainly owing to some limiting effects. Read More

View Article and Full-Text PDF
February 2021

A novel podocyte protein, R3h domain containing-like, inhibits TGF-β-induced p38 MAPK and regulates the structure of podocytes and glomerular basement membrane.

J Mol Med (Berl) 2021 Feb 23. Epub 2021 Feb 23.

Department of Endocrinology, Hematology, and Gerontology, Chiba University Graduate School of Medicine, Chiba, 260-8670, Japan.

Not only in kidney glomerular physiological function but also glomerular pathology especially in diabetic condition, glomerular podocytes play pivotal roles. Therefore, it is important to increase our knowledge about the genes and proteins expressed in podocytes. Recently, we have identified a novel podocyte-expressed gene, R3h domain containing-like (R3hdml) and analyzed its function in vivo as well as in vitro. Read More

View Article and Full-Text PDF
February 2021

Vincristine leads to colonic myenteric neurons injury via pro-inflammatory macrophages activation.

Biochem Pharmacol 2021 Feb 19:114479. Epub 2021 Feb 19.

Department of Physiology, School of Basic Medical Sciences, Cheeloo Medical College, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong, 250012, P.R. China; Provincial Key Lab of Mental Disorders, Shandong University, Jinan, Shandong, 250012, P.R. China. Electronic address:

Vincristine is widely used in treatment of various malignant tumors. The clinical application of vincristine is accompanied by peripheral neurotoxicity which might not be strictly related to the mechanism of anti-tumor action. There are several possible mechanisms but the effect of vincristine on enteric neurons and the underlying mechanism are still unclear. Read More

View Article and Full-Text PDF
February 2021

Hydroxychavicol, a polyphenol from leaf extract, induces cell cycle arrest and apoptosis in -resistant HT-29 colon cancer cells.

J Zhejiang Univ Sci B 2021 Feb;22(2):112-122

Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.

This study aims to elucidate the antiproliferative mechanism of hydroxychavicol (HC). Its effects on cell cycle, apoptosis, and the expression of c-Jun N-terminal kinase (JNK) and P38 mitogen-activated protein kinase (MAPK) in HT-29 colon cancer cells were investigated. HC was isolated from leaf (PBL) and verified by high-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR), and gas chromatography-mass spectrometry (GC-MS). Read More

View Article and Full-Text PDF
February 2021