Thrombin Receptor-Activating Protein (TRAP)-Activated Akt Is Involved in the Release of Phosphorylated-HSP27 (HSPB1) from Platelets in DM Patients.

Abstract

It is generally known that heat shock protein 27 (HSP27) is phosphorylated through p38 mitogen-activated protein (MAP) kinase. We have previously reported that HSP27 is released from human platelets associated with collagen-induced phosphorylation. In the present study, we conducted an investigation into the effect of thrombin receptor-activating protein (TRAP) on the release of HSP27 in platelets in type 2 diabetes mellitus (DM) patients. The phosphorylated-HSP27 levels induced by TRAP were directly proportional to the aggregation of platelets. The levels of phosphorylated-HSP27 (Ser-78) were correlated with the levels of phosphorylated-p38 MAP kinase and phosphorylated-Akt in the platelets stimulated by 10 µM TRAP but not with those of phosphorylated-p44/p42 MAP kinase. The levels of HSP27 released from the TRAP (10 µM)-stimulated platelets were correlated with the levels of phosphorylated-HSP27 in the platelets. The released platelet-derived growth factor-AB (PDGF-AB) levels were in parallel with the HSP27 levels released from the platelets stimulated by 10 µM TRAP. Although the area under the curve (AUC) of small aggregates (9-25 µm) induced by 10 µM TRAP showed no significant correlation with the released HSP27 levels, AUC of medium aggregates (25-50 µm), large aggregates (50-70 µm) and light transmittance were significantly correlated with the released HSP27 levels. TRAP-induced phosphorylation of HSP27 was truly suppressed by deguelin, an inhibitor of Akt, in the platelets from a healthy subject. These results strongly suggest that TRAP-induced activation of Akt in addition to p38 MAP kinase positively regulates the release of phosphorylated-HSP27 from human platelets, which is closely related to the platelet hyper-aggregation in type 2 DM patients.

• Authors: Haruhiko Tokuda, Gen Kuroyanagi, Masanori Tsujimoto, Rie Matsushima-Nishiwaki, Shigeru Akamatsu, Yukiko Enomoto, Hiroki Iida, Takanobu Otsuka, Shinji Ogura, Toru Iwama, Kumi Kojima, Osamu Kozawa
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 17 Issue 5 (May 14 2016) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 27187380 (Publication Type: Journal Article)

Chemical References

• HSP27 Heat-Shock Proteins
• HSPB1 protein, human
• Heat-Shock Proteins
• Molecular Chaperones
• Oligopeptides
• Platelet-Derived Growth Factor
• platelet-derived growth factor AB
• thrombin receptor-activating peptide SFLLRNPNDKY
• Rotenone
• Proto-Oncogene Proteins c-akt
• Extracellular Signal-Regulated MAP Kinases
• p38 Mitogen-Activated Protein Kinases
• deguelin

Topics

• Aged
• Area Under Curve
• Blood Platelets (drug effects, metabolism)
• Diabetes Mellitus, Type 2 (blood, enzymology)
• Enzyme Activation (drug effects)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Female
• HSP27 Heat-Shock Proteins (metabolism)
• Heat-Shock Proteins
• Humans
• Male
• Molecular Chaperones
• Oligopeptides (pharmacology)
• Phosphorylation (drug effects)
• Platelet Aggregation (drug effects)
• Platelet-Derived Growth Factor (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rotenone (analogs & derivatives, pharmacology)
• p38 Mitogen-Activated Protein Kinases (metabolism)