The effects of ER stress on protein secretion by cardiac myocytes are not well understood. In this study, the ER stressor thapsigargin (TG), which depletes ER calcium, induced death of cultured neonatal rat ventricular myocytes (NRVMs) in high media volume but fostered protection in low media volume. In contrast, another ER stressor, tunicamycin (TM), a protein glycosylation inhibitor, induced NRVM death in all media volumes, suggesting that protective proteins were secreted in response to TG but not TM. Proteomic analyses of TG- and TM-conditioned media showed that the secretion of most proteins was inhibited by TG and TM; however, secretion of several ER-resident proteins, including GRP78 was increased by TG but not TM. Simulated ischemia, which decreases ER/SR calcium also increased secretion of these proteins. Mechanistically, secreted GRP78 was shown to enhance survival of NRVMs by collaborating with a cell-surface protein, CRIPTO, to activate protective AKT signaling and to inhibit death-promoting SMAD2 signaling. Thus, proteins secreted during ER stress mediated by ER calcium depletion can enhance cardiac myocyte viability.

• Klíčová slova
• Cardiac myocyte death, Cardiokine, Cardioprotection, ER stress, Heart failure, Proteostasis,
• MeSH
• apoptóza MeSH
• autokrinní signalizace MeSH
• biologické markery MeSH
• chaperon endoplazmatického retikula BiP MeSH
• epidermální růstový faktor metabolismus   MeSH
• kardiomyocyty účinky léků   metabolismus   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• membránové glykoproteiny metabolismus   MeSH
• myši MeSH
• náchylnost k nemoci MeSH
• nádorové proteiny metabolismus   MeSH
• parakrinní signalizace MeSH
• proteom * MeSH
• proteomika * metody   MeSH
• sarkoplazmatické retikulum metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• stres endoplazmatického retikula * účinky léků   MeSH
• thapsigargin farmakologie   MeSH
• vápník metabolismus   MeSH
• vápníková signalizace účinky léků   MeSH
• viabilita buněk MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• biologické markery MeSH
• chaperon endoplazmatického retikula BiP MeSH
• epidermální růstový faktor MeSH
• Hspa5 protein, mouse MeSH Prohlížeč
• membránové glykoproteiny MeSH
• nádorové proteiny MeSH
• proteom * MeSH
• Tdgf1 protein, mouse MeSH Prohlížeč
• thapsigargin MeSH
• vápník MeSH