Naslov
Reactive oxygen species generation is independent of de novo sphingolipids in apoptotic photosenzitized cells

Autori
Dolgachev, Vladislav ; Nagy, Biserka ; Taffe, Bonita ; Hanada, Kentaro ; Šeparović, Duška

Izvornik
Experimental Cell Research (0014-4827) 288 (2003), 2; 425-436

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
apoptosis; oxidative stress; ; ; m; MnTBAP; Pc4; photodynamic therapy; sphingolipids; superoxide

Sažetak
Our recent studies have shown that the de novo spingolipids play a role in apoptosis of photosensitized cells. To elucidate the involvement of the de novo sphingolipids in reactive oxygen species (ROS) production and mitochondrial depolarization during apoptosis, the stess inducer photodynamic therapy (PDT) with the photosensitizer Pc 4 was used. In Jurkat cells PDT-triggered ROS production or mitochondrial membrane potential (&#61508 ; ; &#61561 ; ; m) loss was not prevented by the de novo sphingolipid synthesis inhibitor ISP-1. However, PDT-C16-ceramide led to enhanced mitochondrial depolarization and DEVDase activation. The superoxide dismutase mimic manganese (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) protected Jurkat cells from ROS generation and apoptosis, but not from &#61508 ; ; &#61561 ; ; m reduction. Spinghanine or C16-ceramide counteracted MnTBAP-induced protection from apoptosis in Jurkat, as well as CHO cells. In LY-B cells, CHO-derived mutants deficient in serine palmitoyltransferase (SPT) activity and the de novo sphingolipid synthesis, mitochondrial depolarization, but not ROS generation, was suppressed post-PDT. In LY-B cells transfected with the SPT component LCB1, &#61508 ; ; &#61561 ; ; m collapse post-PDT was restored. The data support that: MnTBAP protects against apoptosis via steps downstream of &#61508 ; ; &#61561 ; ; m loss ; de novo sphingolipids are not required for ROS generation, but can play a role in &#61508 ; ; &#61561 ; ; m dissipation in photosensitized apoptotic cells.

Izvorni jezik
Engleski

Znanstvena područja
Javno zdravstvo i zdravstvena zaštita

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