GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Acylated Ghrelin Protects the Hearts of Rats from Doxorubicin-Induced Fas/FasL Apoptosis by Stimulating SERCA2a Mediated by Activation of PKA and Akt.
Shati. Ali A AA; Dallak. M M
Key Findings
- Acylated ghrelin improves heart contractility and reduces structural damage in rats treated with doxorubicin.
- The protective effect involves increased SERCA2a activity, activation of PKA and Akt, and suppression of Fas/FasL‑mediated apoptosis.
- Using the ghrelin‑receptor antagonist D‑Lys3‑GHRP‑6 or inhibitors of PKA/Akt eliminates the cardioprotective benefits, confirming the pathway’s importance.
Practical Outcomes
- For the biohacking community, the study hints that ghrelin‑type agonists could someday support heart health under stress, but the work is limited to rats and a specific chemotherapy toxin. No human dosing or safety data are provided, so it’s not ready for personal protocols yet. More research is needed before considering ghrelin‑based supplements for cardioprotection.
Summary
In rats, giving the hormone-like peptide acylated ghrelin helped keep the heart healthy when the animals were exposed to a chemotherapy drug that normally damages heart cells. The protection came from better calcium handling in heart cells and turning off a cell‑death signal, and it required the ghrelin receptor and the signaling proteins PKA and Akt. Blocking the receptor with a ghrelin‑related peptide (D‑Lys3‑GHRP‑6) stopped the benefit.
Abstract
This study investigated if the cardioprotective effect of acylated ghrelin (AG) against doxorubicin (DOX)-induced cardiac toxicity in rats involves inhibition of Fas/FasL-mediated cell death. It also investigated if such an effect is mediated by restoring Ca<sup>+2</sup> homeostasis from the aspect of stimulation of SERCA2a receptors. Adult male Wistar rats were divided into 4 groups (20 rats/each) as control, control + AG, DOX, and DOX + AG. AG was co-administered to all rats consecutively for 35 days. In addition, isolated cardiomyocytes were cultured and treated with AG in the presence or absence of DOX with or without pre-incubation with [D-Lys3]-GHRP-6 (a AG receptor antagonist), VIII (]an Akt inhibitor), or KT-5720 (a PKA inhibitor). AG increased LVSP, dp/dt<sub>max</sub>, and dp/dt<sub>min</sub> in both control and DOX-treated animals and improved cardiac ultrastructural changes in DOX-treated rats. It also inhibited ROS in control rats and lowered LVEDP, intracellular levels of ROS and Ca<sup>2+</sup>, and activity of calcineurin in LVs of DOX-treated rats. Concomitantly, it inhibited LV NFAT-4 nuclear translocation and downregulated their protein levels of Fas and FasL. Mechanistically, in control or DOX-treated hearts or cells, AG upregulated the levels of SERCA2a and increased the activities of PKA and Akt, leading to increase phosphorylation of phospholamban at Ser<sup>16</sup> and Thr<sup>17</sup>. All these effects were abolished by D-Lys3-GHRP-6, VIII, or KT-5720 and were independent of food intake or GH/IGF-1. In conclusion, AG cardioprotection against DOX involves inhibition of extrinsic cell death and restoring normal Ca<sup>+2</sup> homeostasis.
Study Information
pubmed
2019
2019-05-15T00:00:00.000Z
10.1007/s12012-019-09527-8
10
80