Induction of the interferon-inducible RNA-degrading enzyme, RNase L, by stress-inducing agents in the human cervical carcinoma cells.

Abstract

RNA-degradation is one of the fundamental mechanisms of interferon (IFN)-inducible antiviral response in mammalian cells. This is primarily brought about by the IFN-inducible 2',5'-oligoadenylate (2-5A)-cofactor dependent ribonuclease L (RNase L). RNase L also functions as a tumor suppressor gene in case of prostate cancer due to its role in apoptosis. We report that RNase L is induced by stress-inducing agents such as double-stranded RNA [poly(I:C)], chemotherapeutic drugs, hydrogen peroxide (H(2)O(2)), calcium chloride (CaCl(2)) and tumor necrosis factor-alpha (TNF) in the human cervical carcinoma (HeLa) cells. The level of RNase L was not detected in the untreated cells. Induction of RNase L by such stress-inducing agents correlated with degradation of cellular RNA, fragmentation of chromatin-DNA and induction of apoptosis. We checked the stress-inducible transcription factor, nuclear factor kappa B (NF-kappaB), which was persistently activated by cycloheximide but not by other agents after 24 hours indicating no role of NFkappaB in the RNase L-induction. However, as expected, TNF-induced NF-kappaB activity was stimulated within 10-30 minutes through degradation of IkappaB-alpha. Our results strongly suggest that the IFN-inducible RNase L is induced by a broad range of stress-inducing signals such as double-stranded RNA (dsRNA) produced during viral infection, membrane- and osmotic shock caused by CaCl(2) and oxidative stress induced by H(2)O(2), inflammation stimulated by TNF-alpha and chemotherapy. Thus, in addition to its antiviral function, the IFN-inducible RNase L may play an important role during stress-response through RNA-degradation and apoptosis.

• Authors: Mitali Pandey, Gagan Deep Bajaj, Pramod C Rath
• Journal: RNA biology (RNA Biol) Vol. 1 Issue 1 Pg. 21-7 (May 2004) ISSN: 1555-8584 [Electronic] United States
• PMID: 17200614 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• NF-kappa B
• RNA, Double-Stranded
• RNA
• Interferons
• Endoribonucleases
• 2-5A-dependent ribonuclease
• Calcium Chloride
• Poly I-C

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis
• Calcium Chloride (pharmacology)
• Carcinoma (enzymology)
• Endoribonucleases (metabolism)
• Female
• Humans
• Interferons (metabolism)
• NF-kappa B (metabolism)
• Oxidative Stress
• Poly I-C (pharmacology)
• RNA (chemistry)
• RNA, Double-Stranded (pharmacology)
• Time Factors
• Uterine Cervical Neoplasms (enzymology)