Native and reconstituted HDL activate Stat3 in ventricular cardiomyocytes via ERK1/2: Role of sphingosine-1-phosphate

Abstract

In ventricular cardiomyocytes, addition of S1P to rHDL enhances its therapeutic potential by improving its capacity to activate Stat3. Activation of Stat3 occurs mainly via the S1P constituent and the lipid receptor S1P2 requiring stimulation of ERK1/2 and Src but not p38 MAPK or PI3K. The study underlines the therapeutic potential of tailoring rHDL to confront particular clinical situations.

Therapeutic Potential of HDL in Cardioprotection and Tissue Repair

“…This protective effect has mainly been evaluated by its capacity to counteract the proapoptotic signals such as caspase 3 activation and DNA fragmentation (Frias et al 2010;Theilmeier et al 2006). HDL incubation induces the phosphorylation of phosphoinositide 3-kinase (PI3K)/Akt, extracellular signal-regulated kinase (ERK) 1/2, p38 mitogen-activated protein kinase (p38 MAPK), and the transcription factor signal transducer and activator of transcription 3 (STAT3) (Frias et al 2009). Although the precise mechanism of action has not been completely elucidated, experiments using specific inhibitors have defined their role in counteracting apoptotic signals induced by doxorubicin.…”

“…Data from experiments using pharmacological antagonists specific for S1P1, S1P2, and S1P3 receptors demonstrate an inhibition of the HDL actions. For example, several experiments suggest that S1P3 is involved in PI3K/ Akt signalling and that S1P2 and/or S1P1 might be involved in ERK1/2 and STAT3 signalling (Frias et al 2009;Tao et al 2010). S1P2 was shown to play a key role in the HDL-induced protection against the apoptotic effects of doxorubicin (Frias et al 2010).…”

Is the Good Cholesterol Bad for Prostate cancer?

“…HDL induces the phosphorylation of STAT3 on both tyrosine 705 and serine 727 in ventricular cardio myocytes. [10].…”

Synthesis of Novel Cannabinoid Ligands and Their Use as Anti-Glioma and Anti-Inflammatory Agents

“…113,115 This suggests that cannabinoid receptors may be a novel target for the regulation of STAT3 function via CB1 or CB2 regulation of G αo -c-Src 116 or via a GPR55 regulated G α12/13 -RhoA-ERK-STAT3 pathway. 117 The effect of HB-I-172 on the tumor suppressor protein p53 was determined using the MSD Multiplex Apoptosis Panel which measures levels of p53, p-p53 (Ser 15), cleaved PARP and cleaved caspase-3. Treatment of U-87 MG cells with HB-I-172 caused a significant increase in levels of both total p53 (Figure 3.14) and phospho-p53 (Figure 3.15) beginning 1 hour post treatment and continuing for the duration of the 24 hour experiment.…”

“…113,115 This suggest that CBs may be a novel target for the regulation of STAT3 function via CB1 or CB2 regulation of G αo -c-Src 116 or via a GPR55 regulated G α12/13 -RhoA-ERK-STAT3 pathway. 117 The level of pMEK (Ser 217, 221) showed a significant decline at 6 hours (Figure 2.14), rebounded at 18 hours (though still lower than control), and then significantly decreased at 24 hours. The increases in pMEK, pERK (Thr 202, Tyr 204, Thr 185, Tyr 187), and pSTAT3 (Tyr705) in the 6 to 18 hours time interval may represent a pro-survival response to changes in pAkt and pBAD levels.…”