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Clusterin inhibits Cr(VI)-induced apoptosis via enhancing mitochondrial biogenesis through AKT-associated STAT3 activation in L02 hepatocytes.
Liang, N, Li, S, Liang, Y, Ma, Y, Tang, S, Ye, S, Xiao, F
Ecotoxicology and environmental safety. 2021;:112447
Abstract
Improper treatment of a large amount of industrial waste makes hexavalent chromium [Cr(VI)] seriously pollute the atmosphere, soil and water, and enter the food chain, seriously affecting the health of workers and local residents. We previously proved that Clusterin (CLU) can inhibit the apoptosis of L02 hepatocytes induced by Cr(VI) through mitochondrial pathway, but the associated molecular mechanism has not been further studied. Mitochondrial biogenesis is an important step in mitochondrial damage repair, but the mechanism of mitochondrial biogenesis in Cr(VI)-induced liver toxicity is still unclear. We demonstrated in the present study that Cr(VI) triggered mitochondrial biogenesis dysfunction-associated apoptosis, and CLU delayed Cr(VI)-induced apoptosis by enhancing mitochondrial biogenesis. Signal transducer and activator of transcription 3 (STAT3) was down-regulated in Cr(VI)-induced apoptosis, and CLU may regulate STAT3 via protein kinase B (PKB/AKT) in Cr(VI)-exposed hepatocytes. We used the STAT3 inhibitor C188-9 and the AKT inhibitor Uprosertib to eliminate the anti-apoptotic effect of CLU, and found that CLU inhibited Cr(VI)-induced apoptosis by up-regulating AKT/STAT3 signal. Based on the fact that both AKT and STAT3 are closely related to mitochondrial biogenesis and mitochondrial pathway-associated apoptosis, this study is the first time to link CLU, STAT3, AKT and mitochondrial biogenesis function after Cr(VI) exposure, to further enrich the experimental basis of Cr(VI)-induced hepatotoxicity, clarify the molecular mechanism of CLU helping cells to escape apoptosis, and also suggest that new ways can be sought to prevent and treat Cr(VI)-induced hepatotoxicity by regulating mitochondrial biosynthesis.
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Chromium effects on glucose tolerance and insulin sensitivity in persons at risk for diabetes mellitus.
Ali, A, Ma, Y, Reynolds, J, Wise, JP, Inzucchi, SE, Katz, DL
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2011;(1):16-25
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Abstract
OBJECTIVE To investigate the effects of daily chromium picolinate supplementation on serum measures of glucose tolerance and insulin sensitivity in patients at high risk for type 2 diabetes mellitus. METHODS We conducted a randomized, double-blind, placebo-controlled, modified cross-over clinical trial with 6-month sequences of intervention and placebo followed by a 6-month postintervention assessment. Adult patients with impaired fasting glucose, impaired glucose tolerance, or metabolic syndrome were enrolled. Participants received 6-month sequences of chromium picolinate or placebo at 1 of 2 dosages (500 or 1000 mcg daily). Primary outcome measures were change in fasting plasma glucose, 2-hour plasma glucose during oral glucose tolerance testing, fasting and 2-hour insulin, and homeostasis model assessment of insulin resistance (HOMA-IR). Secondary outcomes included anthropometric measures, blood pressure, endothelial function, hemoglobin A1c, lipids, and urinary microalbumin. RESULTS Fifty-nine participants were enrolled. No changes were seen in glucose level, insulin level, or HOMA-IR (all P>.05) after 6 months of chromium at either dosage level (500 mcg or 1000 mcg daily) when compared with placebo. None of the secondary outcomes improved with either chromium dosage compared with placebo (P>.05). CONCLUSIONS Chromium supplementation does not appear to ameliorate insulin resistance or impaired glucose metabolism in patients at risk for type 2 diabetes and thus is unlikely to attenuate diabetes risk.