Molecular mechanism of polypeptides from Chlamys farreri (PCF)’s anti-apoptotic effect in UVA-exposed HaCaT cells involves HSF1/HSP70, JNK, XO, iNOS and NO/ROS

• HSF1/HSP70 is involved in PCF’s anti-apoptotic effect against UVA-induced apoptosis.
• Inhibition of JNK also is involved and is likely mediated via HSF1/HSP70 activation.
• Inhibition of iNOS expression is likely part of the mechanism of PCF.
• Xanthine oxidase is involved in PCF’s anti-apoptotic effect.
• NO/ROS release is altered by PCF treatment and is likely part of the mechanism.

This study investigated the molecular mechanisms of polypeptides from Chlamys farreri (PCF)’s anti-apoptotic effects in ultraviolet A-rays (UVA) exposed HaCaT cells. UVA-induced apoptosis in HaCaT cells was confirmed with Hoechst 33258 fluorescent staining; PCF treatment inhibited UVA-induced apoptosis in HaCaT cells, increased transcriptional activities of heat shock factor protein 1 (HSF1) and the expression of heat shock protein 70 (HSP70), whereas inhibited activation of c-Jun N-terminal kinases (JNK), expression of xanthine oxidese (XO), inducible nitric oxide synthase (iNOS) and release of nitric oxide (NO)/reactive oxygen species (ROS). Meanwhile, the HSF1 transcription inhibitor quercetin increased UVA-induced apoptosis, activation of JNK, expression of XO and iNOS and release of NO/ROS. Among the two NO release peaks we found in UVA exposed HaCaT cells, XO inhibitor oxypurinol was found to be able to inhibit NO release at 3 h post UVA exposure but not 18 h, while iNOS inhibitor S-methylisothiourea sulfate (SMT) was found to inhibit iNOS expression and NO release at 18 h but not 3 h. PCF’s protection against UVA-induced apoptosis in HaCaT cells involves increased transcriptional activity of HSF1, increased expression of HSP70, and the subsequential inhibition of JNK pathway, XO and iNOS expression and ROS/NO release.