DMSO modulates the pathway of apoptosis triggering

Abstract

Abstract:We demonstrate here that distribution of caspase-9 influences the pathway of apoptosis triggering, since caspase-9 is activated efficiently only when it is distributed solely in the cytosol. Caspase-9 moves to the nuclei in a response to cell stress during isolation of primary hepatocytes; this is called preapoptotic cell stress response. The dimethyl sulfoxide (DMSO) treatment cannot prevent the migration of caspase-9 into the nuclei when it is added to primary hepatocytes immediately after isolation; however, it can trigger redistribution of caspase-9 from the nuclei into the cytosol when added 1 day post-isolation. This redistribution is temporary, since caspase-9 returns to the nuclei within 48 hours of DMSO treatment. Thereafter, some caspase-9 is retained in the nuclei of DMSO-treated hepatocytes for longer than in the nuclei of untreated hepatocytes. By measuring caspase activities, we demonstrate that the addition of DMSO to cell culture medium can temporarily normalize the susceptibility of hepatocytes for apoptosis triggering through the intrinsic pathway. DMSO contributes also to the prolonged pathway inactivation, i.e., by extending preapoptotic cell stress response. We propose that DMSO extends the survival of primary hepatocytes by modulating preapoptotic cell stress response, which could be exploited for extending the lifespan of other primary cell cultures.

Kualitas Sperma Beku Sapi Bali dalam Pengencer Air Kelapa Modifikasi dengan Berbagai Aras Dimethyl Sulfoxide (FROZEN SPERM QUALITY OF BALI BULLS IN MODIFIED COCONUT WATER EXTENDER WITH DIFFERENT DIMETHYL SULFOXIDE CONCENTRATION)

“…Senyawa DMSO dengan konsentrasi dan suhu pemaparan yang tidak tepat dapat menyebabkan protein unfolding (Arakawa et al, 2007) dan peningkatan fluiditas membran sel (Gurtovenko et al, 2007). Konsentrasi DMSO yang tinggi dapat menghancurkan struktur membran bilayer (Wang et al, 2007), apoptosis pada sel limfoma (Liu et al, 2001) dan osteoklas (Lemieux et al, 2011); sedangkan pada konsentrasi rendah dapat mencegah apoptosis pada sel hepatosit tikus (Banic et al, 2011). Kadar DMSO yang tidak tepat juga dapat menghambat respirasi mitokondria dan peningkatan kalsium sistolik (Ivanov, 2001).…”

Review-Influence of Nanomaterials on Cellular Stress, and Cellular Behavior

“…Cell under stress may modulate the signaling pathways like mammalian target of rapamycin, transformation of related protein-53, Necrotic factor kappa β, or may exhibit adaptive behavior with respect to the stress [18][19][20][21][22]. The stress can induce genomic instability or production of those proteins that are responsible for the protection of the cell or the disintegration of existing proteins and/or hinder their functions.…”

Aging, Oxidative Stress and Antioxidants

“…It may inactivate the activation of apoptosis through caspase-9, i.e. through the intrinsic pathway, one of the main apoptotic pathways [70,117]. Early stress responses result also in the post-translational activation of pre-existing defenses, as well as activation of signal transduction pathways that initiate late responses, namely the de novo synthesis of stress proteins and antioxidant defenses [65].…”