Heng M C, Song M K, Harker J, Heng M K
Division of Dermatology, Department of Medicine, UCLA San Fernando Valley Program, VA Greater Los Angeles Healthcare System (Sepulveda), 16111 Plummer Street, Sepulveda, CA 91343, USA.
Br J Dermatol. 2000 Nov;143(5):937-49. doi: 10.1046/j.1365-2133.2000.03767.x.
Phosphorylase kinase (PhK), also known as adenosine triphosphate (ATP)-phosphorylase b phosphotransferase, integrates multiple calcium/calmodulin-dependent signalling pathways, including those involved in cell migration and cell proliferation, while coupling these pathways to glycogenolysis and ATP-dependent phosphorylation, thus ensuring continuing energy supply for these activities.
Our laboratory recently reported correlation of elevated PhK activity with psoriatic activity. This study further evaluates the significance of drug-induced suppression of PhK activity on psoriatic activity.
PhK activity was assayed in four groups, each with 10 patients: (i) active untreated psoriasis; (ii) resolving psoriasis treated by calcipotriol (Dovonex(R), Bristol Myers Squibb, Princeton, NJ, U.S.A. ), a vitamin D3 analogue and an indirect inhibitor of PhK; (iii) curcumin (diferuloylmethane), a selective PhK inhibitor; and (iv) 10 normal non-psoriatic subjects.
PhK activity in units mg-1 protein was highest in active untreated psoriasis (1204 +/- 804.3; mean +/- SD), lower in the calcipotriol-treated group (550.7 +/- 192. 9), lower in curcumin-treated group (207.2 +/- 97.6), and lowest in normal skin (105.4 +/- 44.6). One-way analysis of variance performed on log-transformed PhK activity measure showed significant differences among the four groups, F3,36 = 48.79, P < 0.0001. Decreased PhK activity in curcumin-and calcipotriol-treated psoriasis was associated with corresponding decreases in keratinocyte transferrin receptor (TRR) expression, severity of parakeratosis and density of epidermal CD8+ T cells.
Our results demonstrate that drug-induced suppression of PhK activity is associated with resolution of psoriatic activity as assessed by clinical, histological and immunohistochemical criteria, and support the hypothesis that effective antipsoriatic activity may be achieved through modulation of PhK activity.
磷酸化酶激酶（PhK），也被称为三磷酸腺苷（ATP）-磷酸化酶b磷酸转移酶，整合多种钙/钙调蛋白依赖性信号通路，包括那些参与细胞迁移和细胞增殖的信号通路，同时将这些通路与糖原分解及ATP依赖性磷酸化相偶联，从而确保为这些活动持续提供能量。
我们实验室最近报道了PhK活性升高与银屑病活动度之间的相关性。本研究进一步评估药物诱导的PhK活性抑制对银屑病活动度的意义。
对四组患者进行PhK活性检测，每组10例：（i）未经治疗的活动性银屑病患者；（ii）接受卡泊三醇（达力士，美国新泽西州普林斯顿市百时美施贵宝公司生产）治疗的缓解期银屑病患者，卡泊三醇是一种维生素D3类似物，也是PhK的间接抑制剂；（iii）姜黄素（二阿魏酰甲烷），一种选择性PhK抑制剂；（iv）10名正常非银屑病受试者。
以每毫克蛋白的酶活性单位计算，未经治疗的活动性银屑病患者的PhK活性最高（1204±804.3；均值±标准差），卡泊三醇治疗组较低（550.7±192.9），姜黄素治疗组更低（207.2±97.6），正常皮肤中最低（105.4±44.6）。对经对数转换的PhK活性测量值进行单因素方差分析显示，四组之间存在显著差异，F3,36 = 48.79，P < 0.0001。姜黄素和卡泊三醇治疗的银屑病患者中PhK活性降低与角质形成细胞转铁蛋白受体（TRR）表达相应降低、角化不全的严重程度及表皮CD8 + T细胞密度降低相关。
我们的结果表明，药物诱导的PhK活性抑制与根据临床、组织学和免疫组化标准评估的银屑病活动度缓解相关，并支持通过调节PhK活性可能实现有效抗银屑病活性这一假说。
