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- W2064222568 abstract "Heme oxygenase-1 (HO-1) is a membrane protein upregulated in response to oxidative stress that confers cardioprotection. The therapeutic potential of HO-1 can be assessed by examining cardiomyocytes survival and function using cobalt protoporphyrin (CoPP) or tin protoporphyrin (SnPP) to increase or inhibit HO-1 activity, respectively. Whether altered HO-1 function affects cardiomyocyte contractility, however, is unknown. Thus, we determined the effects of CoPP (n=11), SnPP (n=15), or PBS (control, n=15) on in vitro single intact adult cardiomyocyte contraction and relaxation using video microscopy and calcium imaging (IonOptix) at 0.5, 1 and 2Hz. At 0.5Hz there was no difference in the rate or magnitude of shortening between groups, and all cells had similar fractional shortening (FS) normalized to peak calcium (FS/Ca2+). FS/Ca2+ was, however, greater at 1Hz and 2Hz in SnPP-treated cells, while CoPP- and PBS-treated cells maintained similar FS/Ca2+ relationships across frequencies (p<0.05). Intriguingly, while SnPP-treated cells increased contraction at faster pacing, only 53% of those cells contracting at 0.5Hz beat synchronously at 1Hz, compared to 100% of CoPP-treated cells and 80% of PBS-treated cells. This difference became more pronounced at 2Hz, as only 26% of SnPP-treated cells and 60% of PBS treated cells able to follow stimulation, while 100% of CoPP-treated cells continued to beat synchronously. Similarly, although time to 90% relaxation was not different between groups at 0.5Hz, it was significantly faster in CoPP- vs. SnPP-treated cells at 2Hz (p<0.05). These results suggest that increasing HO-1 activity via CoPP treatment maintains cell viability under stress, while SnPP- induced HO-1 inhibition reduces survivability at higher pacing frequencies. The mechanisms behind this action are unknown, but may be partially due to HO-1-induced calcium desensitization of the myofilament. Supported by NSF GRFP (SGN) and NIH HL086709 (MA, MR)." @default.
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- W2064222568 date "2010-01-01" @default.
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- W2064222568 title "Contractile Function is Altered by Regulation of HO-1 Activity in Single Adult Rat Cardiomyocytes" @default.
- W2064222568 doi "https://doi.org/10.1016/j.bpj.2009.12.3943" @default.
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