DNAJA4 deficiency augments hyperthermia-induced Clusterin and ERK activation: two critical protective factors of human keratinocytes from hyperthermia-induced injury.

BACKGROUND: Hyperthermia upregulates DNAJA4, a member of heat shock proteins (HSPs) 40 family, in human keratinocytes and HPV-infected tissue. DNAJA4 deficiency enhances growth arrest induced by hyperthermia. Clusterin (CLU) and phosphorylated ERK (p-ERK) play a role in regulating cell proliferation and apoptosis, under environmental stress. OBJECTIVES: To examine the downstream molecules and signalling pathways of DNAJA4 and assess their roles in cell cycle and apoptosis of keratinocytes in response to hyperthermia. METHODS: Wild-type and DNAJA4-knockout (KO) HaCaT cells were exposed to either 44 °C (hyperthermia) or 37 °C (control) for 30 min. The expression levels of CLU and p-ERK were determined by RT-PCR and Western blotting. RNAi and PD98059 were used to inhibit the expression of CLU and p-ERK, respectively. Cell viability, cell cycle and apoptosis were analysed by MTS assay and flow cytometry. Fresh biopsy samples of human normal foreskin or condyloma acuminatum (CA) were utilized to examine the expression of CLU and p-ERK after ex vivo culture at 44 °C. RESULTS: The expression of CLU and p-ERK was significantly increased by hyperthermia treatment at 44 °C in HaCaT cells, foreskin and HPV-infected tissues. In HaCaT cells subjected to hyperthermia, DNAJA4 deficiency further augmented the expression of CLU and p-ERK. CLU deficiency enhanced the p-ERK expression. Hyperthermia-induced CLU and p-ERK exerted protective roles mainly through inhibiting apoptosis and maintaining cell cycle, respectively. CONCLUSIONS: In keratinocytes, CLU and p-ERK are induced by hyperthermia, an effect which can be further enhanced by DNAJA4 deficiency. CLU deficiency also increases p-ERK expression. Both CLU and p-ERK are critical protective factors of human keratinocytes from hyperthermia-induced injury.

[Protective effect of RenShen compound and DanHuang compound on muscle atrophy in suspended rats].

OBJECTIVE: To study the protective effect of RenShen compound and DanHuang compound on muscle atrophy caused by simulated weightlessness in rats. METHOD: Percentage and cross sectional area of fibers and ultrastructure of soleus (SOL) and gastrocnemius (GAS) were determined in 30 d tail suspended rats with or without administration of the medicine. RESULT: The percentage of type I fiber of SOL in RenShen (RS) group and DanHuang (DH) group increased by (13.5 +/- 0.96)% (P < 0.05) and (11.2 +/- 0.84)% (P < 0.05) respectively, and those of GAS showed only an increasing trend as compared with suspension control (SC). Cross sectional area of muscle fibers of SOL and GAS in both groups increased, especially in RS group (P < 0.05). The construction of SOL sarcomere in RS and DH groups was improved as compared with SC. CONCLUSION: RS and DH compounds can partially prevent muscle atrophy caused by tail suspension.

Studies on atrophic change of soleus muscle and its countermeasures in suspended rat.

In the environment of microgravity, the disused atrophy of skeletal muscle, especially leg's muscle, would occur. The three purposes of this study were: 1. To observe the dynamic changes of disused atrophy of skeletal muscle under simulated weightlessness; 2. To approach the mechanism of disused atrophy of muscle; 3. To approach the countermeasures for reducing the degree of atrophy of muscle.