Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type 4 phosphodiesterase (PDE4) inhibitors reportedly induce apoptosis in chronic lymphocytic leukemia (CLL) cells. Following clinical improvement of one previously untreated CLL patient with sildenafil therapy, we evaluated the in vitro induction of apoptosis in CLL cells by 4 PDE5/6 inhibitors, including sildenafil, vardenafil, zaprinast, and methoxyquinazoline (MQZ). After 24 hours of culture, the various PDE inhibitors differed in their ability to induce apoptosis, with zaprinast displaying no killing effect. Normal B cells isolated from control donors were totally resistant to PDE-induced apoptosis. Vardenafil was 3 and 30 times more potent an inducer of apoptosis than sildenafil and MQZ, respectively. Both vardenafil and sildenafil failed to elevate adenosine 3'5' cyclic monophosphate (cAMP) levels, largely excluding an inhibitory effect on cAMP-PDE3, -PDE4, and -PDE7. Vardenafil- or sildenafil-treated B-CLL cells displayed up to 30% intracellular active caspase 3. Drug-induced apoptosis was inhibited by the caspase inhibitor z-VAD.fmk, prevented by interleukin-4 (IL-4), and significantly reduced by stromal-derived factor1-alpha (SDF-1alpha). We conclude that vardenafil and sildenafil induce caspase-dependent apoptosis of B-CLL cells in vitro and thus might be considered in the treatment of CLL patients. However, further in vivo investigations should be warranted.
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PMID:Sildenafil and vardenafil, types 5 and 6 phosphodiesterase inhibitors, induce caspase-dependent apoptosis of B-chronic lymphocytic leukemia cells. 1239 51

Apoptosis of vascular smooth muscle cells plays an important role in vascular calcification (VC). However, the potential mechanism remains poorly understood. Previous studies showed that apoptosis mediated by endoplasmic reticulum stress (ERS) participates in several diseases with VC. We prepared two rat models of calcification, vitamin D(3) plus nicotine (VDN) and rapid calcification (RC), to investigate whether ERS-mediated apoptosis is activated in VC. TUNEL staining and cleaved caspase 3 protein levels illustrated enhanced apoptosis in calcification groups. Western blot analysis revealed the ERS hallmarks GRP78 and GRP94 increased by 43.9% and 91.7%, respectively, in the VDN group and GRP78 elevated by 84.0% in the RC group (all P<0.05) as compared with controls. Moreover, two molecules of ERS-induced apoptosis, caspase 12 and C/EBP homologous protein, were up-regulated nearly 3-fold (P<0.05) in the VDN group and 10-fold (P<0.01) in the RC group. Our results indicated that ERS-induced apoptosis may be involved in VC, and amelioration of ERS could be a novel strategy to prevent and treat the related diseases.
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PMID:Endoplasmic reticulum stress-mediated apoptosis is activated in vascular calcification. 1962 43