Osmotic stress, not aldose reductase activity, directly induces growth factors and MAPK signaling changes during sugar cataract formation.
Osmotic stress, not aldose reductase activity, directly induces growth factors and MAPK signaling changes during sugar cataract formation.
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DOI：
10.1016/j.exer.2012.05.007
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发表时间：
2012-08
影响因子：
3.4
通讯作者：
Kador, Peter F.
中科院分区：
文献类型：
--
作者：
Zhang, Peng;Xing, Kuiyi;Randazzo, James;Blessing, Karen;Lou, Marjorie F.;Kador, Peter F.
关键词：
在大鼠糖性白内障形成过程中，醛糖还原酶（AR）活性不仅与透镜状山梨醇（糖尿病）或半乳糖醇（半乳糖）的形成有关，还与信号转导改变、细胞毒性信号和细胞凋亡激活有关。利用体外和体内技术，研究了AR活性、多元醇（山梨醇和半乳糖醇）形成、渗透胁迫、生长因子诱导和细胞信号传导变化之间的相互关系。在体外研究中，将Sprague Dawley大鼠的晶体在tc -199-碳酸氢盐培养基中培养48小时，培养基中含有30mm果糖（对照），或30mm葡萄糖或半乳糖，含/不含醛糖还原酶抑制剂AL1576或tolrestat，山梨糖醇脱氢酶抑制剂（SDI） CP-470,711或15mm甘露醇（渗透补偿培养基）。在体内研究中，从链脲佐菌素诱导的糖尿病大鼠（Sprague Dawley）中获得晶状体，这些大鼠喂食加/不加ARIs AL1576或托瑞司他10周。正如预期的那样，在高葡萄糖/半乳糖培养基中培养的晶状体或来自未经治疗的糖尿病大鼠的晶状体均显示出GSH池的减少，而ARI治疗则减少了这种减少。糖尿病大鼠或葡萄糖/半乳糖培养条件下的晶状体显示碱性fgf、TGF-β的表达增加，通过P-Akt、P-ERK1/2和P-SAPK/JNK的信号传导增加，这些信号也被ARIs归一化到非糖尿病对照组的表达水平。在含有30mm葡萄糖或半乳糖的体代偿培养基中培养大鼠晶状体不会导致生长因子表达增加或信号传导改变。这些研究表明，晶状体对渗透胁迫的生物物理反应导致晶状体内碱性fgf和TGF-β的产生增加，并在糖性白内障形成过程中观察到细胞毒性信号的改变。
In sugar cataract formation in rats, aldose reductase (AR) actitvity is not only linked to lenticular sorbitol (diabetic) or galactitol (galactosemic) formation but also to signal transduction changes, cytotoxic signals and activation of apoptosis. Using both in vitro and in vivo techniques, the interrelationship between AR activity, polyol (sorbitol and galactitol) formation, osmotic stress, growth factor induction, and cell signaling changes have been investigated. For in vitro studies, lenses from Sprague Dawley rats were cultured for up to 48 hrs in TC-199-bicarbonate media containing either 30 mM fructose (control), or 30 mM glucose or galctose with/without the aldose reductase inhibitors AL1576 or tolrestat, the sorbitol dehydrogenase inhibitor (SDI) CP-470,711, or 15 mM mannitol (osmotic-compensated media). For in vivo studies, lenses were obtained from streptozotocin-induced diabetic Sprague Dawley rats fed diet with/without the ARIs AL1576 or tolrestat for 10 weeks. As expected, lenses cultured in high glucose / galactose media or from untreated diabetic rats all showed a decrease in the GSH pool that was lessened by ARI treatment. Lenses either from diabetic rats or from glucose/galactose culture conditions showed increased expression of basic-FGF, TGF-β, and increased signaling through P-Akt, P-ERK1/2 and P-SAPK/JNK which were also normalized by ARIs to the expression levels observed in non-diabetic controls. Culturing rat lenses in osomotically compensated media containing 30 mM glucose or galactose did not lead to increased growth factor expression or altered signaling. These studies indicate that it is the biophysical response of the lens to osmotic stress that results in an increased intralenticular production of basic-FGF and TGF-β and the altered cytotoxic signaling that is observed during sugar cataract formation.
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影响因子：
9.8
作者：
CHENG, HM;GONZALEZ, RG
通讯作者：
GONZALEZ, RG
DOI：
10.1097/01.asn.0000077408.15865.06
发表时间：
2003-08-01
影响因子：
13.6
作者：
Chung, SSM;Ho, ECM;Chung, SK
通讯作者：
Chung, SK
影响因子：
2.1
作者：
Jonas, Jost B.;Neumaier, Michael
通讯作者：
Neumaier, Michael
影响因子：
3.4
作者：
Kador, PF;Inoue, J;Sato, S
通讯作者：
Sato, S
影响因子：
2.9
作者：
BRADFORD, MM
通讯作者：
BRADFORD, MM