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Concanamycin A, a Vacuolar Type H(+)-ATPase Inhibitor, Induces Cell Death in Activated CD8(+) CTL

Concanamycin A, a Vacuolar Type H(+)-ATPase Inhibitor, Induces Cell Death in Activated CD8(+) CTL

K Togashi, T Kataoka, K Nagai

Cytotechnology. 1997 Nov;25(1-3):127-35.

PMID: 22358885

Abstract:

Concanamycin A (CMA) and concanamycin B (CMB) are specific inhibitors of vacuolar type H(+)-ATPase (V-ATPase). In our previous studies, intraperitoneal injection of CMB was shown to suppress the increase in CD8(+) CTL population, but not to affect CD4(+) and B220(+) populations, in mice immunized with allogeneic tumors. To clarify the molecular basis of the selective decrease in the CD8(+) CTL population by CMB, we have performed a series of in vitro experiments with use of CMA. Cell viability of the CD8(+) population prepared from the immunized mice was preferentially decreased by CMA treatment. Moreover, in the CD8(+) CTL clone, CMA induced a marked DNA fragmentation and nuclear condensation characteristic of apoptosis. Anti-CD3 or phorbol ester accelerated the CMA-induced reduction in cell viability of the CD8(+) CTL clone, but not CD4(+) T cell clones. However, this rapid cell death was not accompanied by DNA fragmentation and nuclear condensation. Perforin and granzyme B were unlikely to be involved in such cell death. Thus, our data suggest that V-ATPase activity is essential for survival of CD8(+) CTL especially when activated.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP80890477	Concanamycin A		80890-47-7	Price

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