Nitric oxide induces heat-shock protein 70 expression in vascular smooth muscle cells via activation of heat shock factor 1.

Abstract

Current data suggest that nitric oxide (NO) is a doubleedged sword that could result in relaxation and/or cytotoxicity of vascular smooth muscle cells (SMCs) via cGMPdependent or -independent signal pathways. Stress or heat shock proteins (hsps) have been shown to be augmented in arterial SMCs during acute hypertension and atherosclerosis, both conditions that are believed to correlate with disturbed NO production. In the present study, we demonstrate that NO generated from sodium nitroprusside (SNP), S -nitroso-N -acetylpenicillamine, and spermine/nitric oxide complex leads to hsp70 induction in cultured SMCs. Western blot analysis demonstrated that hsp70 protein expression peaked between 6 and 12 h after treatment with SNP, and elevated protein levels were preceded by induction of hsp70 mRNA within 3 h. Induction of hsp70 mRNA was associated with the activation of heat shock transcription factor 1 (HSF1), suggesting that the response was regulated at the transcriptional level. HSF1 activation was completely blocked by hemoglobin, dithiothreitol, and cycloheximide, suggesting that the protein damage and nascent polypeptide formation induced by NO may initiate this activation.

Endothelial nitric oxide synthase induces heat shock protein HSPA6 (HSP70B′) in human arterial smooth muscle cells

“…In the present study the observed upregulation of HSP 70-1A and -1B is consistent with a previous report showing NO inducing HSP 70 expression in SMC's via HSF 1 activation [27]. It is thought that the upregulation of HSP 70 is to protect the SMC's from injury as a result of NO stimulation [27].…”

Antiapoptotic effect of haem oxygenase-1 induced by nitric oxide in experimental solid tumour

“…HSP70, which is one of the most important HSPs ubiquitously distributed in mammalian systems (Schlesinger, 1990;Xu et al, 1997), was expressed by AH136B cells and solid tumours. However, although HSP70 has been reported to be induced by NO exposure (Xu et al, 1997), our present analysis of HSP70 with NO donors and NOS inhibitors in vitro and in vivo showed that NO does not participate in HSP70 upregulation in AH136B cells. Thus, we suggest that HSP70 expression in AH136B tumours may be positively regulated by ischaemia or hypoxia through a mechanism different from HO-1 induction involving NO.…”

Interferon-α induces apoptosis in human KB cells through a stress-dependent mitogen activated protein kinase pathway that is antagonized by epidermal growth factor

“…Therefore, onset of apoptosis in cells exposed to IFNa was paralleled by HSP increase which was, in turn, neutralized by EGF. These effects can be explained by the finding that HSPs exert an important protective role in the cells against apoptosis induced by several kinds of damaging agents 14,15,27,28 even if their function is still not completely defined. 13,29 Moreover, growth factors can inhibit both spontaneous 10,12 and injury-mediated apoptosis.…”

“…13,14 In fact, the apoptosis induced by nitric oxyde, a classical shock agent, is prevented by the increased expression of heat shock protein (HSP)-70 in vascular smooth muscle cells. 15 Moreover, it has been reported that a hypoxic stress induces EGF-R upregulation and increases HSP expression in human tumour cells 16 and HSPs themselves confer protection against apoptosis induced by several injuries in cardiocytes and cancer cells. 13,14 Therefore, EGF-R upregulation and stress protein induction could be convergent in the protection from programmed cell death.…”