Load-dependent induction of apoptosis in multicellular myocardial preparations.
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Load-dependent induction of apoptosis in multicellular myocardial preparations. / Janssen, P M L; Hasenfuss, G; Zeitz, Oliver; Lehnart, S E; Prestle, J; Darmer, D; Holtz, J; Schumann, H.
In: AM J PHYSIOL-HEART C, Vol. 282, No. 1, 1, 2002, p. 349-356.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Load-dependent induction of apoptosis in multicellular myocardial preparations.
AU - Janssen, P M L
AU - Hasenfuss, G
AU - Zeitz, Oliver
AU - Lehnart, S E
AU - Prestle, J
AU - Darmer, D
AU - Holtz, J
AU - Schumann, H
PY - 2002
Y1 - 2002
N2 - Increased mechanical load has been proposed as an inductor of apoptosis, but it is unknown whether this can occur in the range of pre- and afterloads that prevail in the beating heart. We investigated apoptosis in cultured rabbit multicellular myocardial preparations over several days. Muscles contracted in absence of pre- and afterload (unloaded isotonic), in absence of preload but in presence of afterload (unloaded isometric), or in presence of both (loaded isometric). After up to 48 h of continuous contractions, apoptosis was assessed by TdT-mediated nick-end labeling (TUNEL) assay and DNA ladder analysis. In muscles that contracted loaded isometric, apoptosis was detected after 6-24 h. After 48 h, apoptosis was most prominent in this group, reflected by a high level of DNA ladder intensity (DLI; 27.8 +/- 11.5), whereas Bcl-xL (on RNA level) was significantly downregulated, and Fas remained unchanged. In unloaded isometric preparations, apoptosis was significantly less (6.9 +/- 5.9 DLI) and very similar to those contracting unloaded isotonic (6.1 +/- 5.1 DLI). We conclude that load-dependent apoptosis can occur at sarcomere lengths achievable in vivo and may mainly result from increased preload.
AB - Increased mechanical load has been proposed as an inductor of apoptosis, but it is unknown whether this can occur in the range of pre- and afterloads that prevail in the beating heart. We investigated apoptosis in cultured rabbit multicellular myocardial preparations over several days. Muscles contracted in absence of pre- and afterload (unloaded isotonic), in absence of preload but in presence of afterload (unloaded isometric), or in presence of both (loaded isometric). After up to 48 h of continuous contractions, apoptosis was assessed by TdT-mediated nick-end labeling (TUNEL) assay and DNA ladder analysis. In muscles that contracted loaded isometric, apoptosis was detected after 6-24 h. After 48 h, apoptosis was most prominent in this group, reflected by a high level of DNA ladder intensity (DLI; 27.8 +/- 11.5), whereas Bcl-xL (on RNA level) was significantly downregulated, and Fas remained unchanged. In unloaded isometric preparations, apoptosis was significantly less (6.9 +/- 5.9 DLI) and very similar to those contracting unloaded isotonic (6.1 +/- 5.1 DLI). We conclude that load-dependent apoptosis can occur at sarcomere lengths achievable in vivo and may mainly result from increased preload.
M3 - SCORING: Zeitschriftenaufsatz
VL - 282
SP - 349
EP - 356
JO - AM J PHYSIOL-HEART C
JF - AM J PHYSIOL-HEART C
SN - 0363-6135
IS - 1
M1 - 1
ER -